{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T16:08:51Z","timestamp":1784909331553,"version":"3.55.0"},"reference-count":109,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T00:00:00Z","timestamp":1732838400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T00:00:00Z","timestamp":1732838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract\u00a0\u62bd\u8c61<\/jats:title><jats:p>Lymphangioleiomyomatosis (LAM) is a rare, slowly progressing, low-grade metastatic tumor primarily affecting women. Currently, vascular endothelial growth factor\u2013D (VEGF-D) is the only validated diagnostic biomarker, enabling diagnosis of LAM without the need for lung biopsy in appropriate clinical settings. However, VEGF-D concentrations are normal in about 30% of patients, rendering it insufficient for diagnosing all cases of LAM. There remains a need to identify more non-invasive, safe, sensitive, and specific biomarkers associated with LAM. Therefore, it is imperative to explore novel non-invasive, safe, and specific diagnostic methods for LAM. This article aims to review biomarkers associated with LAM, including potential biomarkers newly discovered or showing advancements in classical biomarkers widely used in LAM, and discuss their application in LAM diagnosis, assessment of disease severity, prediction of treatment response, and prognosis.\u6dcb\u5df4\u7ba1\u5e73\u6ed1\u808c\u7624\u75c5 \uff08LAM\uff09 \u662f\u4e00\u79cd\u7f55\u89c1\u7684\u3001\u8fdb\u5c55\u7f13\u6162\u7684\u4f4e\u7ea7\u522b\u8f6c\u79fb\u6027\u80bf\u7624\uff0c\u4e3b\u8981\u5f71\u54cd\u5973\u6027\u3002\u76ee\u524d\uff0c\u8840\u7ba1\u5185\u76ae\u751f\u957f\u56e0\u5b50-D \uff08VEGF-D\uff09 \u662f\u552f\u4e00\u7ecf\u8fc7\u9a8c\u8bc1\u7684\u8bca\u65ad\u751f\u7269\u6807\u5fd7\u7269\uff0c\u65e0\u9700\u5728\u9002\u5f53\u7684\u4e34\u5e8a\u73af\u5883\u4e2d\u8fdb\u884c\u80ba\u6d3b\u68c0\u5373\u53ef\u8bca\u65ad LAM\u3002\u7136\u800c\uff0c\u7ea6 30% \u60a3\u8005\u7684 VEGF-D \u6d53\u5ea6\u6b63\u5e38\uff0c\u4e0d\u8db3\u4ee5\u8bca\u65ad\u6240\u6709 LAM \u75c5\u4f8b\u3002\u4ecd\u7136\u9700\u8981\u786e\u5b9a\u4e0e LAM \u76f8\u5173\u7684\u66f4\u591a\u65e0\u521b\u3001\u5b89\u5168\u3001\u654f\u611f\u548c\u7279\u5f02\u6027\u7684\u751f\u7269\u6807\u5fd7\u7269\u3002\u56e0\u6b64\uff0c\u5f53\u52a1\u4e4b\u6025\u662f\u63a2\u7d22\u65b0\u578b\u65e0\u521b\u3001\u5b89\u5168\u548c\u7279\u5f02\u6027\u7684 LAM \u8bca\u65ad\u65b9\u6cd5\u3002\u672c\u6587\u65e8\u5728\u56de\u987e\u4e0e LAM \u76f8\u5173\u7684\u751f\u7269\u6807\u5fd7\u7269\uff0c\u5305\u62ec\u65b0\u53d1\u73b0\u7684\u6f5c\u5728\u751f\u7269\u6807\u5fd7\u7269\u6216\u663e\u793a\u51fa LAM \u4e2d\u5e7f\u6cdb\u4f7f\u7528\u7684\u7ecf\u5178\u751f\u7269\u6807\u5fd7\u7269\u7684\u8fdb\u5c55\uff0c\u5e76\u8ba8\u8bba\u5b83\u4eec\u5728 LAM \u8bca\u65ad\u3001\u75be\u75c5\u4e25\u91cd\u7a0b\u5ea6\u8bc4\u4f30\u3001\u6cbb\u7597\u53cd\u5e94\u9884\u6d4b\u548c\u9884\u540e\u4e2d\u7684\u5e94\u7528\u3002<\/jats:p>","DOI":"10.1186\/s13023-024-03455-9","type":"journal-article","created":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T11:20:31Z","timestamp":1732879231000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The development for emerging biomarkers of lymphangioleiomyomatosis"],"prefix":"10.1186","volume":"19","author":[{"given":"Liting","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6618-690X","authenticated-orcid":false,"given":"Siying","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,29]]},"reference":[{"key":"3455_CR1","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.pharmthera.2015.12.008","volume":"158","author":"LM Moir","year":"2016","unstructured":"Moir LM, Lymphangioleiomyomatosis. Current understanding and potential treatments[J\/OL]. Pharmacol Ther. 2016;158:114\u201324. https:\/\/doi.org\/10.1016\/j.pharmthera.2015.12.008.","journal-title":"Pharmacol Ther"},{"issue":"2","key":"3455_CR2","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1055\/s-0040-1702195","volume":"41","author":"KF Xu","year":"2020","unstructured":"Xu KF, Xu W, Liu S, et al. Lymphangioleiomyomatosis[J\/OL]. Semin Respir Crit Care Med. 2020;41(2):256\u201368. https:\/\/doi.org\/10.1055\/s-0040-1702195.","journal-title":"Semin Respir Crit Care Med"},{"issue":"1","key":"3455_CR3","doi-asserted-by":"publisher","first-page":"5640","DOI":"10.1038\/s41467-020-18979-4","volume":"11","author":"K Obraztsova","year":"2020","unstructured":"Obraztsova K, Basil MC, Rue R, et al. mTORC1 activation in lung mesenchyme drives sex- and age-dependent pulmonary structure and function decline[J\/OL]. Nat Commun. 2020;11(1):5640. https:\/\/doi.org\/10.1038\/s41467-020-18979-4.","journal-title":"Nat Commun"},{"issue":"1","key":"3455_CR4","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s12931-020-1316-3","volume":"21","author":"Q Wang","year":"2020","unstructured":"Wang Q, Luo M, Xiang B, et al. The efficacy and safety of pharmacological treatments for lymphangioleiomyomatosis[J\/OL]. Respir Res. 2020;21(1):55. https:\/\/doi.org\/10.1186\/s12931-020-1316-3.","journal-title":"Respir Res"},{"issue":"9","key":"3455_CR5","doi-asserted-by":"publisher","first-page":"3374","DOI":"10.1210\/en.2016-1395","volume":"157","author":"H Prizant","year":"2016","unstructured":"Prizant H, Hammes SR, Minireview. Lymphangioleiomyomatosis (LAM): the other. Steroid-Sensitive Cancer[J\/OL] Endocrinol. 2016;157(9):3374\u201383. https:\/\/doi.org\/10.1210\/en.2016-1395.","journal-title":"Steroid-Sensitive Cancer[J\/OL] Endocrinol"},{"issue":"1","key":"3455_CR6","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s12931-018-0797-9","volume":"19","author":"ECT Nascimento","year":"2018","unstructured":"Nascimento ECT, do, Baldi BG, Mariani AW, et al. Immunohistological features related to functional impairment in lymphangioleiomyomatosis[J\/OL]. Respir Res. 2018;19(1):83. https:\/\/doi.org\/10.1186\/s12931-018-0797-9.","journal-title":"Respir Res"},{"key":"3455_CR7","doi-asserted-by":"publisher","first-page":"554134","DOI":"10.3389\/fmed.2020.554134","volume":"7","author":"X Song","year":"2020","unstructured":"Song X, Cai H, Yang C, et al. Possible novel therapeutic targets in lymphangioleiomyomatosis Treatment[J\/OL]. Front Med. 2020;7:554134. https:\/\/doi.org\/10.3389\/fmed.2020.554134.","journal-title":"Front Med"},{"issue":"11","key":"3455_CR8","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1016\/S2213-2600(21)00228-9","volume":"9","author":"C McCarthy","year":"2021","unstructured":"McCarthy C, Gupta N, Johnson SR, et al. Lymphangioleiomyomatosis: pathogenesis, clinical features, diagnosis, and management[J\/OL]. Lancet Respiratory Med. 2021;9(11):1313\u201327. https:\/\/doi.org\/10.1016\/S2213-2600(21)00228-9.","journal-title":"Lancet Respiratory Med"},{"issue":"3","key":"3455_CR9","doi-asserted-by":"publisher","first-page":"827","DOI":"10.2214\/ajr.180.3.1800827","volume":"180","author":"M Koyama","year":"2003","unstructured":"Koyama M, Johkoh T, Honda O, et al. Chronic cystic lung disease: diagnostic accuracy of high-resolution CT in 92 Patients[J\/OL]. Am J Roentgenol. 2003;180(3):827\u201335. https:\/\/doi.org\/10.2214\/ajr.180.3.1800827.","journal-title":"Am J Roentgenol"},{"issue":"6","key":"3455_CR10","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1164\/rccm.201607-1384ST","volume":"194","author":"FX McCormack","year":"2016","unstructured":"McCormack FX, Gupta N, Finlay GR, et al. Official American Thoracic Society\/Japanese Respiratory Society Clinical Practice Guidelines: Lymphangioleiomyomatosis diagnosis and Management[J\/OL]. Am J Respir Crit Care Med. 2016;194(6):748\u201361. https:\/\/doi.org\/10.1164\/rccm.201607-1384ST.","journal-title":"Am J Respir Crit Care Med"},{"issue":"11","key":"3455_CR11","doi-asserted-by":"publisher","first-page":"1469","DOI":"10.1016\/j.rmed.2015.09.005","volume":"109","author":"E Radzikowska","year":"2015","unstructured":"Radzikowska E, Jagu\u015b P, Sobiecka M, et al. Correlation of serum vascular endothelial growth factor-D concentration with clinical presentation and course of lymphangioleiomyomatosis[J\/OL]. Respir Med. 2015;109(11):1469\u201375. https:\/\/doi.org\/10.1016\/j.rmed.2015.09.005.","journal-title":"Respir Med"},{"issue":"4","key":"3455_CR12","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.2353\/ajpath.2007.060835","volume":"170","author":"L Kopfstein","year":"2007","unstructured":"Kopfstein L, Veikkola T, Djonov VG, et al. Distinct roles of vascular endothelial growth factor-D in lymphangiogenesis and metastasis[J\/OL]. Am J Pathol. 2007;170(4):1348\u201361. https:\/\/doi.org\/10.2353\/ajpath.2007.060835.","journal-title":"Am J Pathol"},{"issue":"10","key":"3455_CR13","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1097\/01.pas.0000172192.25295.45","volume":"29","author":"T Kumasaka","year":"2005","unstructured":"Kumasaka T, Seyama K, Mitani K, et al. Lymphangiogenesis-mediated shedding of LAM Cell clusters as a mechanism for dissemination in Lymphangioleiomyomatosis[J\/OL]. Am J Surg Pathol. 2005;29(10):1356\u201366. https:\/\/doi.org\/10.1097\/01.pas.0000172192.25295.45.","journal-title":"Am J Surg Pathol"},{"issue":"1","key":"3455_CR14","doi-asserted-by":"publisher","first-page":"8406","DOI":"10.1038\/s41598-021-88064-3","volume":"11","author":"K Nishino","year":"2021","unstructured":"Nishino K, Yoshimatsu Y, Muramatsu T, et al. Isolation and characterisation of lymphatic endothelial cells from lung tissues affected by lymphangioleiomyomatosis[J\/OL]. Sci Rep. 2021;11(1):8406. https:\/\/doi.org\/10.1038\/s41598-021-88064-3.","journal-title":"Sci Rep"},{"issue":"2","key":"3455_CR15","doi-asserted-by":"publisher","first-page":"e0212776","DOI":"10.1371\/journal.pone.0212776","volume":"14","author":"M Hirose","year":"2019","unstructured":"Hirose M, Matsumuro A, Arai T, et al. Serum vascular endothelial growth factor-D as a diagnostic and therapeutic biomarker for lymphangioleiomyomatosis[J\/OL]. PLoS ONE. 2019;14(2):e0212776. https:\/\/doi.org\/10.1371\/journal.pone.0212776.","journal-title":"PLoS ONE"},{"issue":"5","key":"3455_CR16","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1378\/chest.08-1160","volume":"135","author":"CG Glasgow","year":"2009","unstructured":"Glasgow CG, Avila NA, Lin JP, et al. Serum vascular endothelial growth Factor-D levels in patients with lymphangioleiomyomatosis reflect lymphatic Involvement[J\/OL]. Chest. 2009;135(5):1293\u2013300. https:\/\/doi.org\/10.1378\/chest.08-1160.","journal-title":"Chest"},{"issue":"6","key":"3455_CR17","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1016\/S2213-2600(13)70090-0","volume":"1","author":"LR Young","year":"2013","unstructured":"Young LR, Lee HS, Inoue Y, et al. Serum VEGF-D concentration as a biomarker of lymphangioleiomyomatosis severity and treatment response: a prospective analysis of the Multicenter International Lymphangioleiomyomatosis Efficacy of Sirolimus (MILES) trial[J\/OL]. Lancet Respiratory Med. 2013;1(6):445\u201352. https:\/\/doi.org\/10.1016\/S2213-2600(13)70090-0.","journal-title":"Lancet Respiratory Med"},{"issue":"1","key":"3455_CR18","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/1465-9921-13-34","volume":"13","author":"WY Chang","year":"2012","unstructured":"Chang WY, Cane JL, Blakey JD, et al. Clinical utility of diagnostic guidelines and putative biomarkers in lymphangioleiomyomatosis[J\/OL]. Respir Res. 2012;13(1):34. https:\/\/doi.org\/10.1186\/1465-9921-13-34.","journal-title":"Respir Res"},{"key":"3455_CR19","doi-asserted-by":"publisher","unstructured":"Ectd N, Bg B, Aw M, et al. Immunohistological features related to functional impairment in lymphangioleiomyomatosis[J\/OL]. Respir Res. 2018;19(1). https:\/\/doi.org\/10.1186\/s12931-018-0797-9. https:\/\/pubmed.ncbi.nlm.nih.gov\/29739412\/. [2024-10-16].","DOI":"10.1186\/s12931-018-0797-9"},{"issue":"1","key":"3455_CR20","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.chest.2017.05.012","volume":"153","author":"AM Taveira-DaSilva","year":"2018","unstructured":"Taveira-DaSilva AM, Jones AM, Julien-Williams P, et al. Long-term effect of Sirolimus on serum vascular endothelial growth factor D levels in patients with Lymphangioleiomyomatosis[J\/OL]. Chest. 2018;153(1):124\u201332. https:\/\/doi.org\/10.1016\/j.chest.2017.05.012.","journal-title":"Chest"},{"issue":"1","key":"3455_CR21","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.chest.2023.02.026","volume":"164","author":"W Xu","year":"2023","unstructured":"Xu W, Yang C, Cheng C, et al. Determinants of progression and mortality in Lymphangioleiomyomatosis[J\/OL]. Chest. 2023;164(1):137\u201348. https:\/\/doi.org\/10.1016\/j.chest.2023.02.026.","journal-title":"Chest"},{"key":"3455_CR22","doi-asserted-by":"publisher","unstructured":"Carsillo T, Astrinidis A, Henske EP. Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis[J\/OL]. Proceedings of the National Academy of Sciences. 2000;97(11):6085\u20136090. https:\/\/doi.org\/10.1073\/pnas.97.11.6085","DOI":"10.1073\/pnas.97.11.6085"},{"key":"3455_CR23","doi-asserted-by":"publisher","unstructured":"Crooks DM, Pacheco-Rodriguez G, DeCastro RM et al. Molecular and genetic analysis of disseminated neoplastic cells in lymphangioleiomyomatosis[J\/OL]. Proceedings of the National Academy of Sciences. 2004;101(50):17462\u201317467. https:\/\/doi.org\/10.1073\/pnas.0407971101","DOI":"10.1073\/pnas.0407971101"},{"issue":"1","key":"3455_CR24","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1378\/chest.13-1071","volume":"145","author":"X Cai","year":"2014","unstructured":"Cai X, Pacheco-Rodriguez G, Haughey M, et al. Sirolimus decreases circulating lymphangioleiomyomatosis cells in patients with Lymphangioleiomyomatosis[J\/OL]. Chest. 2014;145(1):108\u201312. https:\/\/doi.org\/10.1378\/chest.13-1071.","journal-title":"Chest"},{"issue":"2","key":"3455_CR25","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.chest.2022.02.032","volume":"162","author":"D Elia","year":"2022","unstructured":"Elia D, Torre O, Vasco C, et al. Pulmonary Langerhans Cell Histiocytosis and Lymphangioleiomyomatosis have circulating cells with loss of heterozygosity of the TSC2 Gene[J\/OL]. Chest. 2022;162(2):385\u201393. https:\/\/doi.org\/10.1016\/j.chest.2022.02.032.","journal-title":"Chest"},{"issue":"10","key":"3455_CR26","doi-asserted-by":"publisher","first-page":"1337","DOI":"10.1164\/rccm.201709-1965ST","volume":"196","author":"N Gupta","year":"2017","unstructured":"Gupta N, Finlay GA, Kotloff RM, et al. Lymphangioleiomyomatosis diagnosis and management: high-resolution chest computed Tomography, Transbronchial Lung Biopsy, and Pleural Disease Management. An official American Thoracic Society\/Japanese Respiratory Society Clinical Practice Guideline[J\/OL]. Am J Respir Crit Care Med. 2017;196(10):1337\u201348. https:\/\/doi.org\/10.1164\/rccm.201709-1965ST.","journal-title":"Am J Respir Crit Care Med"},{"issue":"1","key":"3455_CR27","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1152\/physrev.00022.2006","volume":"87","author":"KJ Greenlee","year":"2007","unstructured":"Greenlee KJ, Werb Z, Kheradmand F. Matrix metalloproteinases in Lung: multiple, multifarious, and Multifaceted[J\/OL]. Physiol Rev. 2007;87(1):69\u201398. https:\/\/doi.org\/10.1152\/physrev.00022.2006.","journal-title":"Physiol Rev"},{"issue":"9","key":"3455_CR28","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1016\/s0046-8177(97)90061-7","volume":"28","author":"T Hayashi","year":"1997","unstructured":"Hayashi T, Fleming MV, Stetler-Stevenson WG, et al. Immunohistochemical study of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in pulmonary lymphangioleiomyomatosis (LAM)[J\/OL]. Hum Pathol. 1997;28(9):1071\u20138. https:\/\/doi.org\/10.1016\/s0046-8177(97)90061-7.","journal-title":"Hum Pathol"},{"key":"3455_CR29","doi-asserted-by":"publisher","unstructured":"Matsui K, Takeda K, Yu ZX, et al. Role for activation of matrix metalloproteinases in the pathogenesis of pulmonary lymphangioleiomyomatosis[J\/OL]. Arch Pathol Lab Med. 2000;124(2):267\u201375. https:\/\/doi.org\/10.1043\/0003-9985(2000)124%3C0267:RFAOMM%3E2.0.CO;2.","DOI":"10.1043\/0003-9985(2000)124%3C0267:RFAOMM%3E2.0.CO;2"},{"key":"3455_CR30","doi-asserted-by":"publisher","first-page":"1079317","DOI":"10.3389\/fmed.2023.1079317","volume":"10","author":"E Revilla-L\u00f3pez","year":"2023","unstructured":"Revilla-L\u00f3pez E, Ruiz De Miguel V, L\u00f3pez-Meseguer M, et al. Lymphangioleiomyomatosis: searching for potential biomarkers[J\/OL]. Front Med. 2023;10:1079317. https:\/\/doi.org\/10.3389\/fmed.2023.1079317.","journal-title":"Front Med"},{"issue":"1","key":"3455_CR31","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.rmed.2008.07.017","volume":"103","author":"N Odajima","year":"2009","unstructured":"Odajima N, Betsuyaku T, Nasuhara Y, et al. Matrix metalloproteinases in blood from patients with LAM[J\/OL]. Respir Med. 2009;103(1):124\u20139. https:\/\/doi.org\/10.1016\/j.rmed.2008.07.017.","journal-title":"Respir Med"},{"issue":"5","key":"3455_CR32","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1165\/rcmb.F267","volume":"28","author":"VP Krymskaya","year":"2003","unstructured":"Krymskaya VP, Shipley JM. Lymphangioleiomyomatosis: a complex tale of serum response factor-mediated tissue inhibitor of metalloproteinase-3 regulation[J\/OL]. Am J Respir Cell Mol Biol. 2003;28(5):546\u201350. https:\/\/doi.org\/10.1165\/rcmb.F267.","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"6","key":"3455_CR33","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1007\/s00408-014-9641-2","volume":"192","author":"BG Baldi","year":"2014","unstructured":"Baldi BG, Araujo MS, Freitas CS, G, et al. Evaluation of the extent of Pulmonary cysts and their association with functional variables and serum markers in Lymphangioleiomyomatosis (LAM)[J\/OL]. Lung. 2014;192(6):967\u201374. https:\/\/doi.org\/10.1007\/s00408-014-9641-2.","journal-title":"Lung"},{"issue":"154","key":"3455_CR34","doi-asserted-by":"publisher","first-page":"ra154134","DOI":"10.1126\/scitranslmed.3003840","volume":"4","author":"EA Goncharova","year":"2012","unstructured":"Goncharova EA, Goncharov DA, Fehrenbach M, et al. Prevention of Alveolar Destruction and Airspace Enlargement in a mouse model of pulmonary lymphangioleiomyomatosis (LAM)[J\/OL]. Sci Transl Med. 2012;4(154):ra154134\u2013154134. https:\/\/doi.org\/10.1126\/scitranslmed.3003840.","journal-title":"Sci Transl Med"},{"key":"3455_CR35","doi-asserted-by":"publisher","unstructured":"Golub LM, Ramamurthy NS, McNamara TF, et al. Tetracyclines inhibit connective tissue breakdown: new therapeutic implications for an old family of drugs[J\/OL]. Critical reviews in oral Biology and Medicine. Volume 2. An Official Publication of the American Association of Oral Biologists; 1991. pp. 297\u2013321. https:\/\/doi.org\/10.1177\/10454411910020030201.","DOI":"10.1177\/10454411910020030201"},{"issue":"1","key":"3455_CR36","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1590\/s1806-37132013000100002","volume":"39","author":"SP Pimenta","year":"2013","unstructured":"Pimenta SP, Baldi BG, Kairalla RA, et al. Doxycycline use in patients with lymphangioleiomyomatosis: biomarkers and pulmonary function response[J\/OL]. Jornal Brasileiro De Pneumologia: Publicacao Oficial Da Sociedade Brasileira De Pneumologia E Tisilogia. 2013;39(1):5\u201315. https:\/\/doi.org\/10.1590\/s1806-37132013000100002.","journal-title":"Jornal Brasileiro De Pneumologia: Publicacao Oficial Da Sociedade Brasileira De Pneumologia E Tisilogia"},{"issue":"4","key":"3455_CR37","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1183\/09031936.00167413","volume":"43","author":"WYC Chang","year":"2014","unstructured":"Chang WYC, Cane JL, Kumaran M, et al. A 2-year randomised placebo-controlled trial of doxycycline for lymphangioleiomyomatosis[J\/OL]. Eur Respir J. 2014;43(4):1114\u201323. https:\/\/doi.org\/10.1183\/09031936.00167413.","journal-title":"Eur Respir J"},{"issue":"1","key":"3455_CR38","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1111\/j.1476-5381.2011.01344.x","volume":"164","author":"L Moir","year":"2011","unstructured":"Moir L, Ng H, Poniris M, et al. Doxycycline inhibits matrix metalloproteinase-2 secretion from TSC2-null mouse embryonic fibroblasts and lymphangioleiomyomatosis cells: doxycycline inhibits LAM cells[J\/OL]. Br J Pharmacol. 2011;164(1):83\u201392. https:\/\/doi.org\/10.1111\/j.1476-5381.2011.01344.x.","journal-title":"Br J Pharmacol"},{"issue":"2","key":"3455_CR39","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1165\/rcmb.2009-0050OC","volume":"42","author":"PS Lee","year":"2010","unstructured":"Lee PS, Tsang SW, Moses MA, et al. Rapamycin-insensitive up-regulation of MMP2 and other genes in tuberous sclerosis complex 2-deficient lymphangioleiomyomatosis-like cells[J\/OL]. Am J Respir Cell Mol Biol. 2010;42(2):227\u201334. https:\/\/doi.org\/10.1165\/rcmb.2009-0050OC.","journal-title":"Am J Respir Cell Mol Biol"},{"key":"3455_CR40","doi-asserted-by":"crossref","unstructured":"Gibbons E, Taya M, Seger C et al. SAT-141 Glycoprotein NMB (GPNMB) Is Pro-Tumorigenic in TSC2-Null Cancer Cells and Is a Potential Drug Target and Biomarker for Lymphangioleiomyomatosis (LAM)[J\/OL]. Journal of the Endocrine Society, 2020, 4(SAT-141)[2021-10-04]. https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC7207399\/.","DOI":"10.1210\/jendso\/bvaa046.1386"},{"key":"3455_CR41","doi-asserted-by":"publisher","unstructured":"Taya M, Hammes SR. Glycoprotein non-metastatic melanoma protein B (GPNMB) and Cancer: a novel potential therapeutic Target[J\/OL]. Steroids. 2018;133:102\u20137. https:\/\/doi.org\/10.1016\/j.steroids.2017.10.013","DOI":"10.1016\/j.steroids.2017.10.013"},{"key":"3455_CR42","doi-asserted-by":"publisher","first-page":"839","DOI":"10.2147\/OTT.S44906","volume":"6","author":"G Maric","year":"2013","unstructured":"Maric G, Rose AA, Annis MG, et al. Glycoprotein non-metastatic b (GPNMB): a metastatic mediator and emerging therapeutic target in cancer[J\/OL]. OncoTargets Therapy. 2013;6:839\u201352. https:\/\/doi.org\/10.2147\/OTT.S44906.","journal-title":"OncoTargets Therapy"},{"issue":"4","key":"3455_CR43","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1530\/ERC-15-0505","volume":"23","author":"H Prizant","year":"2016","unstructured":"Prizant H, Taya M, Lerman I, et al. Estrogen maintains myometrial tumors in a lymphangioleiomyomatosis model[J\/OL]. Endocrine-related Cancer. 2016;23(4):265\u201380. https:\/\/doi.org\/10.1530\/ERC-15-0505.","journal-title":"Endocrine-related Cancer"},{"key":"3455_CR44","doi-asserted-by":"publisher","unstructured":"Gibbons E, Taya M, Wu H et al. GPNMB promotes tumor growth and is a biomarker for lymphangioleiomyomatosis[J\/OL]. Endocrine-related Cancer, 2024:ERC-23-0312. https:\/\/doi.org\/10.1530\/ERC-23-0312","DOI":"10.1530\/ERC-23-0312"},{"issue":"4","key":"3455_CR45","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1530\/ERC-19-0431","volume":"27","author":"M Taya","year":"2020","unstructured":"Taya M, Garcia-Hernandez M, de la Rangel-Moreno L. Neutrophil elastase from myeloid cells promotes TSC2-null tumor growth[J\/OL]. Endocrine-related Cancer. 2020;27(4):261\u201374. https:\/\/doi.org\/10.1530\/ERC-19-0431.","journal-title":"Endocrine-related Cancer"},{"issue":"1","key":"3455_CR46","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1038\/modpathol.2011.136","volume":"25","author":"G Martignoni","year":"2012","unstructured":"Martignoni G, Bonetti F, Chilosi M, et al. Cathepsin K expression in the spectrum of perivascular epithelioid cell (PEC) lesions of the kidney[J\/OL]. Mod Pathol. 2012;25(1):100\u201311. https:\/\/doi.org\/10.1038\/modpathol.2011.136.","journal-title":"Mod Pathol"},{"issue":"8","key":"3455_CR47","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.1016\/j.ajpath.2017.04.014","volume":"187","author":"A Dongre","year":"2017","unstructured":"Dongre A, Clements D, Fisher AJ, et al. Cathepsin K in Lymphangioleiomyomatosis: LAM cell-fibroblast interactions enhance protease activity by Extracellular Acidification[J\/OL]. Am J Pathol. 2017;187(8):1750\u201362. https:\/\/doi.org\/10.1016\/j.ajpath.2017.04.014.","journal-title":"Am J Pathol"},{"issue":"2","key":"3455_CR48","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1038\/modpathol.2008.189","volume":"22","author":"M Chilosi","year":"2009","unstructured":"Chilosi M, Pea M, Martignoni G, et al. Cathepsin-k expression in pulmonary lymphangioleiomyomatosis[J\/OL]. Mod Pathol. 2009;22(2):161\u20136. https:\/\/doi.org\/10.1038\/modpathol.2008.189.","journal-title":"Mod Pathol"},{"issue":"3","key":"3455_CR49","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1002\/cjp2.162","volume":"6","author":"S Miller","year":"2020","unstructured":"Miller S, Stewart ID, Clements D, et al. Evolution of lung pathology in lymphangioleiomyomatosis: associations with disease course and treatment response[J\/OL]. J Pathol Clin Res. 2020;6(3):215\u201326. https:\/\/doi.org\/10.1002\/cjp2.162.","journal-title":"J Pathol Clin Res"},{"key":"3455_CR50","doi-asserted-by":"crossref","unstructured":"Duchow EG, Cooke NE, Seeman J et al. Vitamin D binding protein is required to utilize skin-generated vitamin D[J\/OL]. Proceedings of the National Academy of Sciences. 2019;116(49):24527\u201324532[2021-04-10]. https:\/\/pubmed.ncbi.nlm.nih.gov\/31748273\/.","DOI":"10.1073\/pnas.1915442116"},{"issue":"5","key":"3455_CR51","doi-asserted-by":"publisher","first-page":"1801886","DOI":"10.1183\/13993003.01886-2018","volume":"52","author":"HJ Liu","year":"2018","unstructured":"Liu HJ, Henske EP. Vitamin D binding protein: a new biomarker of disease severity in lymphangioleiomyomatosis[J\/OL]. Eur Respir J. 2018;52(5):1801886. https:\/\/doi.org\/10.1183\/13993003.01886-2018.","journal-title":"Eur Respir J"},{"issue":"5","key":"3455_CR52","doi-asserted-by":"publisher","first-page":"1800951","DOI":"10.1183\/13993003.00951-2018","volume":"52","author":"S Miller","year":"2018","unstructured":"Miller S, Coveney C, Johnson J, et al. The vitamin D binding protein axis modifies disease severity in lymphangioleiomyomatosis[J\/OL]. Eur Respir J. 2018;52(5):1800951. https:\/\/doi.org\/10.1183\/13993003.00951-2018.","journal-title":"Eur Respir J"},{"issue":"1","key":"3455_CR53","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1007\/s12551-021-00928-0","volume":"14","author":"Y Senju","year":"2022","unstructured":"Senju Y, Tsai FC. A biophysical perspective of the regulatory mechanisms of ezrin\/radixin\/moesin proteins[J\/OL]. Biophys Rev. 2022;14(1):199\u2013208. https:\/\/doi.org\/10.1007\/s12551-021-00928-0.","journal-title":"Biophys Rev"},{"issue":"1","key":"3455_CR54","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s12931-024-02685-6","volume":"25","author":"X Song","year":"2024","unstructured":"Song X, Cai H, Peng W, et al. The role of moesin in diagnosing and assessing severity of lymphangioleiomyomatosis[J\/OL]. Respir Res. 2024;25(1):57. https:\/\/doi.org\/10.1186\/s12931-024-02685-6.","journal-title":"Respir Res"},{"issue":"3","key":"3455_CR55","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/s41581-022-00665-x","volume":"19","author":"R Agoro","year":"2023","unstructured":"Agoro R, White KE. Regulation of FGF23 production and phosphate metabolism by bone-kidney interactions[J\/OL]. Nat Rev Nephrol. 2023;19(3):185\u201393. https:\/\/doi.org\/10.1038\/s41581-022-00665-x.","journal-title":"Nat Rev Nephrol"},{"key":"3455_CR56","doi-asserted-by":"crossref","unstructured":"Esposito A J, Imani J, Shrestha S, et al. Lymphangioleiomyomatosis: circulating levels of FGF23 and pulmonary diffusion[J\/OL]. Jornal Brasileiro De Pneumologia: Publicacao Oficial Da Sociedade Brasileira De Pneumologia E Tisilogia, 2023, 49(2): e20220356. https:\/\/doi.org\/10.36416\/1806-3756\/e20220356.","DOI":"10.36416\/1806-3756\/e20220356"},{"issue":"1","key":"3455_CR57","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.ajpath.2013.04.002","volume":"183","author":"ER Gilbert","year":"2013","unstructured":"Gilbert ER, Eby JM, Hammer AM, et al. Positioning Ganglioside D3 as an immunotherapeutic target in Lymphangioleiomyomatosis[J\/OL]. Am J Pathol. 2013;183(1):226\u201334. https:\/\/doi.org\/10.1016\/j.ajpath.2013.04.002.","journal-title":"Am J Pathol"},{"key":"3455_CR58","doi-asserted-by":"publisher","unstructured":"Torre O, Elia D, Caminati A, et al. New insights in lymphangioleiomyomatosis and pulmonary langerhans cell histiocytosis[J\/OL]. Eur Respiratory Review: Official J Eur Respiratory Soc. 2017;26(145). https:\/\/doi.org\/10.1183\/16000617.0042-2017.","DOI":"10.1183\/16000617.0042-2017"},{"issue":"1","key":"3455_CR59","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1165\/rcmb.2011-0215TR","volume":"46","author":"DF Dilling","year":"2012","unstructured":"Dilling DF, Gilbert ER, Picken MM, et al. A current viewpoint of lymphangioleiomyomatosis supporting immunotherapeutic treatment options[J\/OL]. Am J Respir Cell Mol Biol. 2012;46(1):1\u20135. https:\/\/doi.org\/10.1165\/rcmb.2011-0215TR.","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"6","key":"3455_CR60","doi-asserted-by":"publisher","first-page":"2463","DOI":"10.2353\/ajpath.2009.090525","volume":"175","author":"J Klarquist","year":"2009","unstructured":"Klarquist J, Barfuss A, Kandala S, et al. Melanoma-associated antigen expression in lymphangioleiomyomatosis renders tumor cells susceptible to cytotoxic T cells[J\/OL]. Am J Pathol. 2009;175(6):2463\u201372. https:\/\/doi.org\/10.2353\/ajpath.2009.090525.","journal-title":"Am J Pathol"},{"issue":"8","key":"3455_CR61","doi-asserted-by":"publisher","first-page":"e98674","DOI":"10.1172\/jci.insight.98674","volume":"3","author":"HJ Liu","year":"2018","unstructured":"Liu HJ, Lizotte PH, Du H, et al. TSC2-deficient tumors have evidence of T cell exhaustion and respond to anti\u2013PD-1\/anti\u2013CTLA-4 immunotherapy[J\/OL]. JCI Insight. 2018;3(8):e98674. https:\/\/doi.org\/10.1172\/jci.insight.98674.","journal-title":"JCI Insight"},{"issue":"6","key":"3455_CR62","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1165\/rcmb.2018-0123OC","volume":"59","author":"K Maisel","year":"2018","unstructured":"Maisel K, Merrilees MJ, Atochina-Vasserman EN, et al. Immune checkpoint ligand PD-L1 is upregulated in Pulmonary Lymphangioleiomyomatosis[J\/OL]. Am J Respir Cell Mol Biol. 2018;59(6):723\u201332. https:\/\/doi.org\/10.1165\/rcmb.2018-0123OC.","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"1","key":"3455_CR63","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1182\/blood-2017-07-740993","volume":"131","author":"ZY Xu-Monette","year":"2018","unstructured":"Xu-Monette ZY, Zhou J, Young KH. PD-1 expression and clinical PD-1 blockade in B-cell lymphomas[J\/OL]. Blood. 2018;131(1):68\u201383. https:\/\/doi.org\/10.1182\/blood-2017-07-740993.","journal-title":"Blood"},{"issue":"1","key":"3455_CR64","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1146\/annurev-immunol-032414-112049","volume":"34","author":"SH Baumeister","year":"2016","unstructured":"Baumeister SH, Freeman GJ, Dranoff G, et al. Coinhibitory pathways in Immunotherapy for Cancer[J\/OL]. Annu Rev Immunol. 2016;34(1):539\u201373. https:\/\/doi.org\/10.1146\/annurev-immunol-032414-112049.","journal-title":"Annu Rev Immunol"},{"issue":"9","key":"3455_CR65","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1158\/2159-8290.CD-18-0367","volume":"8","author":"SC Wei","year":"2018","unstructured":"Wei SC, Duffy CR, Allison JP. Fundamental mechanisms of Immune Checkpoint Blockade Therapy[J\/OL]. Cancer Discov. 2018;8(9):1069\u201386. https:\/\/doi.org\/10.1158\/2159-8290.CD-18-0367.","journal-title":"Cancer Discov"},{"key":"3455_CR66","doi-asserted-by":"publisher","first-page":"561","DOI":"10.3389\/fphar.2017.00561","volume":"8","author":"HO Alsaab","year":"2017","unstructured":"Alsaab HO, Sau S, Alzhrani R, et al. PD-1 and PD-L1 Checkpoint Signaling Inhibition for Cancer Immunotherapy: mechanism, combinations, and clinical Outcome[J\/OL]. Front Pharmacol. 2017;8:561. https:\/\/doi.org\/10.3389\/fphar.2017.00561.","journal-title":"Front Pharmacol"},{"issue":"1","key":"3455_CR67","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s12890-018-0775-5","volume":"19","author":"J Pluvy","year":"2019","unstructured":"Pluvy J, Brosseau S, Stelianides S, et al. Safe and effective use of nivolumab for treating lung adenocarcinoma associated with sporadic lymphangioleiomyomatosis: a rare case report[J\/OL]. BMC Pulm Med. 2019;19(1):12. https:\/\/doi.org\/10.1186\/s12890-018-0775-5.","journal-title":"BMC Pulm Med"},{"key":"3455_CR68","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.coi.2018.02.004","volume":"51","author":"P Dhar","year":"2018","unstructured":"Dhar P, Wu JD. NKG2D and its ligands in cancer[J\/OL]. Curr Opin Immunol. 2018;51:55\u201361. https:\/\/doi.org\/10.1016\/j.coi.2018.02.004.","journal-title":"Curr Opin Immunol"},{"key":"3455_CR69","doi-asserted-by":"crossref","unstructured":"Marcus A, Gowen BG, Thompson TW et al. Recognition of Tumors by the Innate Immune System and Natural Killer Cells[M\/OL]\/\/Advances in Immunology: Vol. 122. Elsevier, 2014: 91\u2013128[2021-04-12]. https:\/\/pubmed.ncbi.nlm.nih.gov\/24507156\/.","DOI":"10.1016\/B978-0-12-800267-4.00003-1"},{"key":"3455_CR70","doi-asserted-by":"publisher","unstructured":"Hilpert J, Grosse-Hovest L, Gr\u00fcnebach F et al. Comprehensive analysis of NKG2D ligand expression and release in leukemia: implications for NKG2D-mediated NK cell responses[J\/OL]. Journal of Immunology (Baltimore, Md.: 1950). 2012;189(3):1360\u20131371. https:\/\/doi.org\/10.4049\/jimmunol.1200796","DOI":"10.4049\/jimmunol.1200796"},{"key":"3455_CR71","doi-asserted-by":"crossref","unstructured":"Osterburg AR, Nelson RL, Yaniv BZ, et al. NK cell activating receptor ligand expression in lymphangioleiomyomatosis is associated with lung function decline[J\/OL]. JCI Insight. 2016;1(16). https:\/\/pubmed.ncbi.nlm.nih.gov\/27734028\/.","DOI":"10.1172\/jci.insight.87270"},{"key":"3455_CR72","doi-asserted-by":"crossref","unstructured":"Foot RA, Osterburg A,  Nelson R,  et al. NKG2D ligand expression in lymphangioleiomyomatosis. JCI Insight, 2016;1(3), e87270. https:\/\/doi.org\/10.1172\/jci.insight.87270","DOI":"10.1172\/jci.insight.87270"},{"key":"3455_CR73","doi-asserted-by":"crossref","unstructured":"Borchers MT, Terry MA, McCormack FX, et al. NK Cell Activation is Increased in Lymphangioleiomyomatosis. American Journal of Respiratory and Critical Care Medicine, vol. 199, 2019, A4279. https:\/\/doi.org\/10.1164\/ajrccm-conference.2019.199.1_MeetingAbstracts.A4279.","DOI":"10.1164\/ajrccm-conference.2019.199.1_MeetingAbstracts.A4279"},{"issue":"1","key":"3455_CR74","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1111\/j.1365-2567.2007.02760.x","volume":"123","author":"JE Park","year":"2008","unstructured":"Park JE, Wu DY, Prendes M, et al. Fine specificity of natural killer T cells against GD3 ganglioside and identification of GM3 as an inhibitory natural killer T-cell ligand[J\/OL]. Immunology. 2008;123(1):145\u201355. https:\/\/doi.org\/10.1111\/j.1365-2567.2007.02760.x.","journal-title":"Immunology"},{"issue":"35","key":"3455_CR75","doi-asserted-by":"publisher","first-page":"27213","DOI":"10.1074\/jbc.M109.087791","volume":"285","author":"Y Ohkawa","year":"2010","unstructured":"Ohkawa Y, Miyazaki S, Hamamura K, et al. Ganglioside GD3 enhances adhesion signals and augments malignant properties of melanoma cells by recruiting integrins to glycolipid-enriched microdomains[J\/OL]. J Biol Chem. 2010;285(35):27213\u201323. https:\/\/doi.org\/10.1074\/jbc.M109.087791.","journal-title":"J Biol Chem"},{"issue":"1","key":"3455_CR76","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1080\/14653240701762380","volume":"10","author":"JE Park","year":"2008","unstructured":"Park JE, Lu SX, Wu DY, et al. Antibody response to GD3 ganglioside is independent of NKT cells[J\/OL]. Cytotherapy. 2008;10(1):38\u201344. https:\/\/doi.org\/10.1080\/14653240701762380.","journal-title":"Cytotherapy"},{"key":"3455_CR77","doi-asserted-by":"publisher","first-page":"379","DOI":"10.3389\/fimmu.2019.00379","volume":"10","author":"V Mollica Poeta","year":"2019","unstructured":"Mollica Poeta V, Massara M, Capucetti A, et al. Chemokines and chemokine receptors: new targets for Cancer Immunotherapy[J\/OL]. Front Immunol. 2019;10:379. https:\/\/doi.org\/10.3389\/fimmu.2019.00379.","journal-title":"Front Immunol"},{"issue":"6","key":"3455_CR78","doi-asserted-by":"publisher","first-page":"1492","DOI":"10.1158\/0008-5472.CAN-16-2755","volume":"77","author":"Y Cui","year":"2017","unstructured":"Cui Y, Steagall WK, Lamattina AM, et al. Aberrant SYK kinase signaling is essential for Tumorigenesis Induced by TSC2 Inactivation[J\/OL]. Cancer Res. 2017;77(6):1492\u2013502. https:\/\/doi.org\/10.1158\/0008-5472.CAN-16-2755.","journal-title":"Cancer Res"},{"issue":"3","key":"3455_CR79","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.4049\/jimmunol.182.3.1270","volume":"182","author":"G Pacheco-Rodriguez","year":"2009","unstructured":"Pacheco-Rodriguez G, Kumaki F, Steagall WK, et al. Chemokine-enhanced chemotaxis of lymphangioleiomyomatosis cells with mutations in the tumor suppressor TSC2 gene[J\/OL]. J Immunol (Baltimore Md: 1950). 2009;182(3):1270\u20137. https:\/\/doi.org\/10.4049\/jimmunol.182.3.1270.","journal-title":"J Immunol (Baltimore Md: 1950)"},{"key":"3455_CR80","doi-asserted-by":"publisher","unstructured":"4 J, Barfuss A, Kandala S, et al. Melanoma-Associated Antigen expression in Lymphangioleiomyomatosis Renders Tumor Cells Susceptible to cytotoxic T Cells[J\/OL]. Am J Pathol. 2009;175(6):2463\u201372. https:\/\/doi.org\/10.2353\/ajpath.2009.090525.","DOI":"10.2353\/ajpath.2009.090525"},{"issue":"1","key":"3455_CR81","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1165\/rcmb.2014-0224OC","volume":"53","author":"EN Atochina-Vasserman","year":"2015","unstructured":"Atochina-Vasserman EN, Guo CJ, Abramova E, et al. Surfactant dysfunction and lung inflammation in the female mouse model of Lymphangioleiomyomatosis[J\/OL]. Am J Respir Cell Mol Biol. 2015;53(1):96\u2013104. https:\/\/doi.org\/10.1165\/rcmb.2014-0224OC.","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"8","key":"3455_CR82","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/nri3024","volume":"11","author":"A Mantovani","year":"2011","unstructured":"Mantovani A, Cassatella MA, Costantini C, et al. Neutrophils in the activation and regulation of innate and adaptive immunity[J\/OL]. Nat Rev Immunol. 2011;11(8):519\u201331. https:\/\/doi.org\/10.1038\/nri3024.","journal-title":"Nat Rev Immunol"},{"issue":"9","key":"3455_CR83","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1158\/1541-7786.MCR-17-0003","volume":"15","author":"I Lerman","year":"2017","unstructured":"Lerman I, Garcia-Hernandez M, de la Rangel-Moreno L. Infiltrating myeloid cells exert protumorigenic actions via Neutrophil Elastase[J\/OL]. Mol Cancer Res. 2017;15(9):1138\u201352. https:\/\/doi.org\/10.1158\/1541-7786.MCR-17-0003.","journal-title":"Mol Cancer Res"},{"issue":"9","key":"3455_CR84","doi-asserted-by":"publisher","first-page":"3356","DOI":"10.1172\/JCI80005","volume":"125","author":"D Marvel","year":"2015","unstructured":"Marvel D, Gabrilovich DI. Myeloid-derived suppressor cells in the tumor microenvironment: expect the unexpected[J\/OL]. J Clin Invest. 2015;125(9):3356\u201364. https:\/\/doi.org\/10.1172\/JCI80005.","journal-title":"J Clin Invest"},{"issue":"8","key":"3455_CR85","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1007\/s00262-012-1294-5","volume":"61","author":"CA Dumitru","year":"2012","unstructured":"Dumitru CA, Moses K, Trellakis S, et al. Neutrophils and granulocytic myeloid-derived suppressor cells: immunophenotyping, cell biology and clinical relevance in human oncology[J\/OL]. Cancer Immunol Immunother. 2012;61(8):1155\u201367. https:\/\/doi.org\/10.1007\/s00262-012-1294-5.","journal-title":"Cancer Immunol Immunother"},{"issue":"3","key":"3455_CR86","doi-asserted-by":"publisher","first-page":"e60014","DOI":"10.1371\/journal.pone.0060014","volume":"8","author":"AJ Trindade","year":"2013","unstructured":"Trindade AJ, Medvetz DA, Neuman NA, et al. MicroRNA-21 is Induced by Rapamycin in a model of tuberous sclerosis (TSC) and Lymphangioleiomyomatosis (LAM)[J\/OL]. PLoS ONE. 2013;8(3):e60014. https:\/\/doi.org\/10.1371\/journal.pone.0060014.","journal-title":"PLoS ONE"},{"issue":"17","key":"3455_CR87","doi-asserted-by":"publisher","first-page":"1768","DOI":"10.1056\/NEJMp058190","volume":"353","author":"CZ Chen","year":"2005","unstructured":"Chen CZ. MicroRNAs as oncogenes and Tumor Suppressors[J\/OL]. N Engl J Med. 2005;353(17):1768\u201371. https:\/\/doi.org\/10.1056\/NEJMp058190.","journal-title":"N Engl J Med"},{"key":"3455_CR88","unstructured":"Singer CA, Barnett SD, Grubbs J et al. miR-25 Targeting Tuberous Sclerosis Complex 1 (TSC1) Expression In Lymphangioleiomyomatosis Cells. American Journal of Respiratory and Critical Care Medicine, vol. 187, 2013, A2027. https:\/\/doi.org\/10.1164\/ajrccm-conference.2013.187.1_MeetingAbstracts.A2027."},{"issue":"2","key":"3455_CR89","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.3892\/or.2018.6916","volume":"41","author":"J Liu","year":"2019","unstructured":"Liu J, Yuan J, Feng T, et al. miR\u2013124 targets retinoid X receptor \u03b1 to reduce growth of TSC2\u2013deficient lymphangioleiomyomatosis[J\/OL]. Oncol Rep. 2019;41(2):1342\u201350. https:\/\/doi.org\/10.3892\/or.2018.6916.","journal-title":"Oncol Rep"},{"key":"3455_CR90","doi-asserted-by":"crossref","unstructured":"Takimoto T, Takeda Y, Koba T et al. MicroRNA Profiles of Serum Extracellular Vesicles in Lymphangioleiomyomatosis. American Journal of Respiratory and Critical Care Medicine, vol. 201, 2020, A4971. https:\/\/doi.org\/10.1164\/ajrccm-conference.2020.201.1_MeetingAbstracts.A4971.","DOI":"10.1164\/ajrccm-conference.2020.201.1_MeetingAbstracts.A4971"},{"issue":"49","key":"3455_CR91","doi-asserted-by":"publisher","first-page":"7367","DOI":"10.1038\/s41388-019-0957-5","volume":"38","author":"HJ Liu","year":"2019","unstructured":"Liu HJ, Lam HC, Baglini CV, et al. Rapamycin-upregulated miR-29b promotes mTORC1-hyperactive cell growth in TSC2-deficient cells by downregulating tumor suppressor retinoic acid receptor \u03b2 (RAR\u03b2)[J\/OL]. Oncogene. 2019;38(49):7367\u201383. https:\/\/doi.org\/10.1038\/s41388-019-0957-5.","journal-title":"Oncogene"},{"issue":"2","key":"3455_CR92","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1165\/rcmb.2023-0243LE","volume":"70","author":"RL Rossi","year":"2024","unstructured":"Rossi RL, Elia D, Torre O, et al. Identification of lymphangioleiomyomatosis-associated serum MicroRNAs[J\/OL]. Am J Respir Cell Mol Biol. 2024;70(2):146\u20138. https:\/\/doi.org\/10.1165\/rcmb.2023-0243LE.","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"1","key":"3455_CR93","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1165\/rcmb.2014-0379RC","volume":"53","author":"C Priolo","year":"2015","unstructured":"Priolo C, Ricoult SJH, Khabibullin D, et al. Tuberous sclerosis complex 2 loss increases Lysophosphatidylcholine Synthesis in Lymphangioleiomyomatosis[J\/OL]. Am J Respir Cell Mol Biol. 2015;53(1):33\u201341. https:\/\/doi.org\/10.1165\/rcmb.2014-0379RC.","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"8","key":"3455_CR94","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1136\/thoraxjnl-2019-214241","volume":"75","author":"L Bottolo","year":"2020","unstructured":"Bottolo L, Miller S, Johnson SR. Sphingolipid, fatty acid and phospholipid metabolites are associated with disease severity and mTOR inhibition in lymphangioleiomyomatosis[J\/OL]. Thorax. 2020;75(8):679\u201388. https:\/\/doi.org\/10.1136\/thoraxjnl-2019-214241.","journal-title":"Thorax"},{"issue":"2","key":"3455_CR95","doi-asserted-by":"publisher","first-page":"76","DOI":"10.21037\/atm-22-6420","volume":"11","author":"W Gu","year":"2023","unstructured":"Gu W, Pan Y, Zhao W, et al. Metabolic signatures of lymphangioleiomyomatosis in biofluids: nuclear magnetic resonance (NMR)-based metabonomics of blood plasma: a case-control study[J\/OL]. Annals Translational Med. 2023;11(2):76. https:\/\/doi.org\/10.21037\/atm-22-6420.","journal-title":"Annals Translational Med"},{"issue":"1","key":"3455_CR96","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1084\/jem.20131080","volume":"211","author":"C Li","year":"2014","unstructured":"Li C, Lee PS, Sun Y, et al. Estradiol and mTORC2 cooperate to enhance prostaglandin biosynthesis and tumorigenesis in TSC2-deficient LAM cells[J\/OL]. J Exp Med. 2014;211(1):15\u201328. https:\/\/doi.org\/10.1084\/jem.20131080.","journal-title":"J Exp Med"},{"issue":"10","key":"3455_CR97","doi-asserted-by":"publisher","first-page":"e104809","DOI":"10.1371\/journal.pone.0104809","volume":"9","author":"C Li","year":"2014","unstructured":"Li C, Zhang E, Sun Y, et al. Rapamycin-insensitive Up-Regulation of adipocyte phospholipase A2 in tuberous sclerosis and Lymphangioleiomyomatosis[J\/OL]. PLoS ONE. 2014;9(10):e104809. https:\/\/doi.org\/10.1371\/journal.pone.0104809.","journal-title":"PLoS ONE"},{"issue":"10","key":"3455_CR98","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1158\/1541-7786.MCR-17-0077","volume":"15","author":"C Li","year":"2017","unstructured":"Li C, Liu X, Liu Y, et al. Tuberin regulates prostaglandin receptor\u2013mediated viability, via Rheb, in mTORC1-Hyperactive Cells[J\/OL]. Mol Cancer Res. 2017;15(10):1318\u201330. https:\/\/doi.org\/10.1158\/1541-7786.MCR-17-0077.","journal-title":"Mol Cancer Res"},{"key":"3455_CR99","doi-asserted-by":"publisher","unstructured":"El-Chemaly S, Taveira-DaSilva A, Bagwe S, et al. Celecoxib in lymphangioleiomyomatosis: results of a phase I clinical trial[J\/OL]. Eur Respir J. 2020;55(5). https:\/\/doi.org\/10.1183\/13993003.02370-2019.","DOI":"10.1183\/13993003.02370-2019"},{"issue":"2","key":"3455_CR100","doi-asserted-by":"publisher","first-page":"76","DOI":"10.21037\/atm-22-6420","volume":"11","author":"W Gu","year":"2023","unstructured":"Gu W, Pan Y, Zhao W, et al. Metabolic signatures of lymphangioleiomyomatosis in biofluids: nuclear magnetic resonance (NMR)-based metabonomics of blood plasma: a case-control study[J\/OL]. Annals Translational Med. 2023;11(2):76\u201376. https:\/\/doi.org\/10.21037\/atm-22-6420.","journal-title":"Annals Translational Med"},{"issue":"5","key":"3455_CR101","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1016\/j.chest.2018.08.1029","volume":"154","author":"AM Lamattina","year":"2018","unstructured":"Lamattina AM, Taveira-Dasilva A, Goldberg HJ, et al. Circulating biomarkers from the phase 1 trial of Sirolimus and Autophagy Inhibition for patients with Lymphangioleiomyomatosis[J\/OL]. Chest. 2018;154(5):1070\u201382. https:\/\/doi.org\/10.1016\/j.chest.2018.08.1029.","journal-title":"Chest"},{"issue":"2","key":"3455_CR102","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.chest.2017.05.018","volume":"153","author":"CG Glasgow","year":"2018","unstructured":"Glasgow CG, Pacheco-Rodriguez G, Steagall WK, et al. CA-125 in Disease Progression and Treatment of Lymphangioleiomyomatosis[J\/OL]. Chest. 2018;153(2):339\u201348. https:\/\/doi.org\/10.1016\/j.chest.2017.05.018.","journal-title":"Chest"},{"key":"3455_CR103","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1186\/1476-4598-13-129","volume":"13","author":"M Felder","year":"2014","unstructured":"Felder M, Kapur A, Gonzalez-Bosquet J, et al. MUC16 (CA125): tumor biomarker to cancer therapy, a work in progress[J\/OL]. Mol Cancer. 2014;13:129. https:\/\/doi.org\/10.1186\/1476-4598-13-129.","journal-title":"Mol Cancer"},{"issue":"1","key":"3455_CR104","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/s13023-019-1050-4","volume":"14","author":"AM Lamattina","year":"2019","unstructured":"Lamattina AM, Poli S, Kidambi P, et al. Serum endostatin levels are associated with diffusion capacity and with tuberous sclerosis- associated lymphangioleiomyomatosis[J\/OL]. Orphanet J Rare Dis. 2019;14(1):72. https:\/\/doi.org\/10.1186\/s13023-019-1050-4.","journal-title":"Orphanet J Rare Dis"},{"key":"3455_CR105","doi-asserted-by":"publisher","DOI":"10.23736\/S0026-4806.21.07322-5","author":"M D\u2019Alessandro","year":"2021","unstructured":"D\u2019Alessandro M, Bergantini L, Cameli P, et al. Prognostic role of KL-6 in lymphangioleiomyomatosis patients[J\/OL]. Minerva Med. 2021. https:\/\/doi.org\/10.23736\/S0026-4806.21.07322-5.","journal-title":"Minerva Med"},{"issue":"1","key":"3455_CR106","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.resinv.2012.02.001","volume":"50","author":"N Ishikawa","year":"2012","unstructured":"Ishikawa N, Hattori N, Yokoyama A, et al. Utility of KL-6\/MUC1 in the clinical management of interstitial lung diseases[J\/OL]. Respiratory Invest. 2012;50(1):3\u201313. https:\/\/doi.org\/10.1016\/j.resinv.2012.02.001.","journal-title":"Respiratory Invest"},{"key":"3455_CR107","doi-asserted-by":"publisher","first-page":"844914","DOI":"10.3389\/fimmu.2022.844914","volume":"13","author":"X Liu","year":"2022","unstructured":"Liu X, Xu Y, Wu X, et al. Soluble Immune-related proteins as new candidate serum biomarkers for the diagnosis and progression of Lymphangioleiomyomatosis[J\/OL]. Front Immunol. 2022;13:844914. https:\/\/doi.org\/10.3389\/fimmu.2022.844914.","journal-title":"Front Immunol"},{"key":"3455_CR108","doi-asserted-by":"publisher","unstructured":"Li M, Zhu WY, Wang J et al. Diagnostic performance of VEGF-D for lymphangioleiomyomatosis: a meta-analysis[J\/OL]. Jornal Brasileiro De Pneumologia: Publicacao Oficial Da Sociedade Brasileira De Pneumologia E Tisilogia. 2022;48(1):e20210337. https:\/\/doi.org\/10.36416\/1806-3756\/e20210337","DOI":"10.36416\/1806-3756\/e20210337"},{"issue":"11","key":"3455_CR109","doi-asserted-by":"publisher","first-page":"1912","DOI":"10.1513\/AnnalsATS.201605-335OC","volume":"13","author":"T Takada","year":"2016","unstructured":"Takada T, Mikami A, Kitamura N, et al. Efficacy and safety of long-term Sirolimus Therapy for Asian patients with Lymphangioleiomyomatosis[J\/OL]. Annals Am Thorac Soc. 2016;13(11):1912\u201322. https:\/\/doi.org\/10.1513\/AnnalsATS.201605-335OC.","journal-title":"Annals Am Thorac Soc"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-024-03455-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-024-03455-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-024-03455-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T12:09:32Z","timestamp":1732882172000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-024-03455-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,29]]},"references-count":109,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["3455"],"URL":"https:\/\/doi.org\/10.1186\/s13023-024-03455-9","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,29]]},"assertion":[{"value":"19 July 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 November 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 November 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent was given by the participants, and all the participants have given the consent for their images.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"445"}}