{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T22:57:54Z","timestamp":1794265074538,"version":"4.9.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T00:00:00Z","timestamp":1685491200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T00:00:00Z","timestamp":1685491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81902984, 81974314, 82072362, 82002223"],"award-info":[{"award-number":["81902984, 81974314, 82072362, 82002223"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81902984, 81974314, 82072362, 82002223"],"award-info":[{"award-number":["81902984, 81974314, 82072362, 82002223"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81902984, 81974314, 82072362, 82002223"],"award-info":[{"award-number":["81902984, 81974314, 82072362, 82002223"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81902984, 81974314, 82072362, 82002223"],"award-info":[{"award-number":["81902984, 81974314, 82072362, 82002223"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shanghai Public Health System Construction Three-Year Action Plan","award":["GWV-10.1-XK04"],"award-info":[{"award-number":["GWV-10.1-XK04"]}]},{"DOI":"10.13039\/501100014175","name":"Shanghai Municipal Health and Family Planning Commission","doi-asserted-by":"crossref","award":["20204Y0070"],"award-info":[{"award-number":["20204Y0070"]}],"id":[{"id":"10.13039\/501100014175","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Respir Res"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background and aims<\/jats:title>\n                <jats:p>This study aimed to investigate the expression of plasma versican and plasma exosomal versican in non-small cell lung cancer (NSCLC) and its correlation with clinicopathological features, and to evaluate its diagnostic performance in NSCLC and its predictive function for NSCLC incidence and metastasis risk.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Materials and methods<\/jats:title>\n                <jats:p>There were 110 instances of NSCLC, 42 cases of benign lung disease, and 55 healthy controls from September 2018 to October 2020 at Tongji Hospital Affiliated to Tongji University. Blood was collected and plasma was separated before surgery, and plasma exosomes were extracted by ExoQuick kit. Morphological and molecular phenotype identification of exosomes was performed by transmission electron microscopy, Nanosight particle tracking analysis, and western blotting. Plasma versican and plasma exosomal versican were detected in all subjects to assess their expression levels and diagnostic value in NSCLC. Clinicopathological data were collected to explore correlations between abnormal plasma versican and plasma exosomal versican expression and clinicopathological parameters. Receiver operating characteristic (ROC) curve was used to judge its diagnostic performance in NSCLC, and binary logistic regression analysis was used to predict the risk of NSCLC incidence and metastasis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Plasma versican and plasma exosomal versican expression in NSCLC patients was significantly upregulated and was significantly higher in T3\u2009+\u2009T4 patients compared with T1\u2009+\u2009T2 patients (P\u2009&lt;\u20090.05); the levels of plasma versican and plasma exosomal versican were positively correlated with lymph node metastasis, distant metastases (e.g., brain, bone), and mutation(e.g., EGFR,ALK)in NSCLC patients (all P\u2009&lt;\u20090.05). Furthermore, ROC curve analysis showed that plasma versican and plasma exosomal versican had higher AUC values than NSE, CYFRA21-1, and SCC, and better diagnostic performance in NSCLC patients. However, the AUC and diagnostic performances of plasma versican and plasma exosomal versican in advanced-stage NSCLC patients were not shown to be significantly better than CEA. The results of binary logistic regression analysis showed that high levels of plasma exosomal versican had higher predictive value for lung cancer incidence, while high levels of plasma versican had higher predictive value for lung cancer metastasis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Our findings showed that plasma versican and plasma exosomal versican might be potential diagnostic markers for NSCLC. High plasma exosomal versican expression can be used as a predictor of NSCLC risk and high plasma versican expression can be used as a predictor of NSCLC metastasis risk.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12931-023-02423-4","type":"journal-article","created":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T05:02:07Z","timestamp":1685509327000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Plasma versican and plasma exosomal versican as potential diagnostic markers for non-small cell lung cancer"],"prefix":"10.1186","volume":"24","author":[{"given":"Wenjing","family":"Chang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jichao","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianyu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anquan","family":"Shang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zujun","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqiang","family":"Quan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,5,31]]},"reference":[{"key":"2423_CR1","doi-asserted-by":"crossref","unstructured":"Siegel RL, Miller KD, Fuchs HE, Jemal A, Cancer Statistics. 2021. CA Cancer J Clin. 2021 Jan;71(1):7\u201333.","DOI":"10.3322\/caac.21654"},{"key":"2423_CR2","doi-asserted-by":"crossref","unstructured":"Alexander M, Kim SY, Cheng H, Update. 2020: Management of Non-Small Cell Lung Cancer. Lung. 2020 Dec;198(6):897\u2013907.","DOI":"10.1007\/s00408-020-00407-5"},{"issue":"10066","key":"2423_CR3","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/S0140-6736(16)30958-8","volume":"389","author":"FR Hirsch","year":"2017","unstructured":"Hirsch FR, Scagliotti GV, Mulshine JL, Kwon R, Curran WJ Jr, Wu YL, Paz-Ares L. Lung cancer: current therapies and new targeted treatments. Lancet. 2017;389(10066):299\u2013311.","journal-title":"Lancet"},{"issue":"9","key":"2423_CR4","doi-asserted-by":"publisher","first-page":"3347","DOI":"10.1172\/JCI80007","volume":"125","author":"S Shalapour","year":"2015","unstructured":"Shalapour S, Karin M. Immunity, inflammation, and cancer: an eternal fight between good and evil. J Clin Invest. 2015;125(9):3347\u201355.","journal-title":"J Clin Invest"},{"issue":"2","key":"2423_CR5","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1007\/s10555-015-9570-4","volume":"34","author":"L Shi","year":"2015","unstructured":"Shi L, Wang L, Hou J, Zhu B, Min Z, Zhang M, Song D, Cheng Y, Wang X. Targeting roles of inflammatory microenvironment in lung cancer and metastasis. Cancer Metastasis Rev. 2015;34(2):319\u201331.","journal-title":"Cancer Metastasis Rev"},{"issue":"11","key":"2423_CR6","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1038\/nm.3394","volume":"19","author":"DF Quail","year":"2013","unstructured":"Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med. 2013;19(11):1423\u201337.","journal-title":"Nat Med"},{"issue":"11","key":"2423_CR7","first-page":"763","volume":"68","author":"S Islam","year":"2020","unstructured":"Islam S, Watanabe H, Versican. A dynamic Regulator of the Extracellular Matrix. J HistochemCytochem. 2020;68(11):763\u201375.","journal-title":"J HistochemCytochem"},{"issue":"12","key":"2423_CR8","first-page":"871","volume":"68","author":"A Papadas","year":"2020","unstructured":"Papadas A, Arauz G, Cicala A, Wiesner J, Asimakopoulos F. Versican and versican-matrikines in Cancer Progression, inflammation, and immunity. J HistochemCytochem. 2020;68(12):871\u201385.","journal-title":"J HistochemCytochem"},{"key":"2423_CR9","doi-asserted-by":"crossref","unstructured":"Asano K, Nelson CM, Nandadasa S, Aramaki-Hattori N, Lindner DJ, Alban T, Inagaki J, Ohtsuki T, Oohashi T, Apte SS, Hirohata S. Stromal Versican regulates Tumor Growth by promoting angiogenesis. Sci Rep. 2017 Dec;8(1):17225.","DOI":"10.1038\/s41598-017-17613-6"},{"key":"2423_CR10","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/978-3-030-48457-6_4","volume":"1272","author":"A Papadas","year":"2020","unstructured":"Papadas A, Asimakopoulos F. Versican in the Tumor Microenvironment. Adv Exp Med Biol. 2020;1272:55\u201372.","journal-title":"Adv Exp Med Biol"},{"key":"2423_CR11","doi-asserted-by":"crossref","unstructured":"Tani H, Sato Y, Ueda M, Miyazaki Y, Suginami K, Horie A, Konishi I, Shinomura T. Role of Versican in the pathogenesis of peritoneal endometriosis. J Clin Endocrinol Metab. 2016 Nov;101(11):4349\u201356.","DOI":"10.1210\/jc.2016-2391"},{"key":"2423_CR12","doi-asserted-by":"crossref","unstructured":"Kim S, Takahashi H, Lin WW, Descargues P, Grivennikov S, Kim Y, Luo JL, Karin M. Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature. 2009 Jan 1;457(7225):102-6.","DOI":"10.1038\/nature07623"},{"issue":"2","key":"2423_CR13","doi-asserted-by":"publisher","first-page":"e56616","DOI":"10.1371\/journal.pone.0056616","volume":"8","author":"D Li","year":"2013","unstructured":"Li D, Wang X, Wu JL, Quan WQ, Ma L, Yang F, Wu KY, Wan HY. Tumor-produced versican V1 enhances hCAP18\/LL-37 expression in macrophages through activation of TLR2 and vitamin D3 signaling to promote Ovarian Cancer Progression in Vitro. PLoS ONE. 2013;8(2):e56616.","journal-title":"PLoS ONE"},{"key":"2423_CR14","doi-asserted-by":"crossref","unstructured":"Ji P, Zhou Y, Yang Y, Wu J, Zhou H, Quan W, Sun J, Yao Y, Shang A, Gu C, Zeng B, Firrman J, Xiao W, Bals R, Sun Z, Li D. Myeloid cell-derived LL-37 promotes lung cancer growth by activating Wnt\/\u03b2-catenin signaling. Theranostics. 2019 Apr 12;9(8):2209\u20132223.","DOI":"10.7150\/thno.30726"},{"key":"2423_CR15","doi-asserted-by":"crossref","unstructured":"Ricciardelli C, Sakko AJ, Ween MP, Russell DL, Horsfall DJ. The biological role and regulation of Versican levels in cancer. Cancer Metastasis Rev. 2009. 28(1\u20132): 233 \u2013 45.","DOI":"10.1007\/s10555-009-9182-y"},{"issue":"4","key":"2423_CR16","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1002\/gcc.22695","volume":"58","author":"E Lianidou","year":"2019","unstructured":"Lianidou E, Pantel K. Liquid biopsies. Genes Chromosomes Cancer. 2019;58(4):219\u201332.","journal-title":"Genes Chromosomes Cancer"},{"key":"2423_CR17","doi-asserted-by":"crossref","unstructured":"Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Sci 2020 Feb 7;367(6478):eaau6977.","DOI":"10.1126\/science.aau6977"},{"issue":"4","key":"2423_CR18","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1172\/JCI81135","volume":"126","author":"R Kalluri","year":"2016","unstructured":"Kalluri R. The biology and function of exosomes in cancer. J Clin Invest. 2016;126(4):1208\u201315. https:\/\/doi.org\/10.1172\/JCI81135.","journal-title":"J Clin Invest"},{"key":"2423_CR19","doi-asserted-by":"crossref","unstructured":"Sun Z, Shi K, Yang S, Liu J, Zhou Q, Wang G, Song J, Li Z, Zhang Z, Yuan W. Effect of exosomal miRNA on cancer biology and clinical applications. Mol Cancer. 2018 Oct;11(1):147.","DOI":"10.1186\/s12943-018-0897-7"},{"key":"2423_CR20","doi-asserted-by":"crossref","unstructured":"Zhang Y, Bi J, Huang J, Tang Y, Du S, Li P, Exosome. A review of its classification, isolation techniques, Storage, Diagnostic and targeted therapy applications. Int J Nanomedicine. 2020 Sep;22:15:6917\u201334.","DOI":"10.2147\/IJN.S264498"},{"key":"2423_CR21","doi-asserted-by":"crossref","unstructured":"Gao H, Cheng Y, Chen Y, Luo F, Shao Y, Sun Z, Bai C. The expression of versican and its role in pancreatic neuroendocrine tumors. Pancreatology. 2020 Jan;20(1):142\u20137.","DOI":"10.1016\/j.pan.2019.11.009"},{"key":"2423_CR22","doi-asserted-by":"crossref","unstructured":"Zhu L, Sun HT, Wang S, Huang SL, Zheng Y, Wang CQ, Hu BY, Qin W, Zou TT, Fu Y, Shen XT, Zhu WW, Geng Y, Lu L, Jia HL, Qin LX, Dong QZ. Isolation and characterization of exosomes for cancer research. J Hematol Oncol. 2020 Nov;10(1):152.","DOI":"10.1186\/s13045-020-00987-y"},{"issue":"7","key":"2423_CR23","doi-asserted-by":"publisher","first-page":"727","DOI":"10.3390\/cells8070727","volume":"8","author":"LM Doyle","year":"2019","unstructured":"Doyle LM, Wang MZ. Overview of Extracellular vesicles, their origin, composition, purpose, and methods for Exosome isolation and analysis. Cells. 2019;8(7):727.","journal-title":"Cells"},{"key":"2423_CR24","unstructured":"Hoshino A, Kim HS, Bojmar L et al. Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers. Cell 2020. 182(4)."},{"key":"2423_CR25","doi-asserted-by":"crossref","unstructured":"Seijo LM, Peled N, Ajona D, Boeri M, Field JK, Sozzi G, Pio R, Zulueta JJ, Spira A, Massion PP, Mazzone PJ, Montuenga LM. Biomarkers in Lung Cancer Screening: achievements, promises, and Challenges. J Thorac Oncol. 2019 Mar;14(3):343\u201357.","DOI":"10.1016\/j.jtho.2018.11.023"},{"key":"2423_CR26","doi-asserted-by":"crossref","unstructured":"Zhangyuan G, Wang F, Zhang H, Jiang R, Tao X, Yu D, Jin K, Yu W, Liu Y, Yin Y, Shen J, Xu Q, Zhang W, Sun B. VersicanV1 promotes proliferation and metastasis of hepatocellular carcinoma through the activation of EGFR-PI3K-AKT pathway. Oncogene. 2020 Feb;39(6):1213\u201330.","DOI":"10.1038\/s41388-019-1052-7"},{"key":"2423_CR27","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.rvsc.2021.08.010","volume":"140","author":"SH Figuer\u00eado","year":"2021","unstructured":"Figuer\u00eado SH, Neto RSC, Ferreira E, Cassali GD, Estrela-Lima A, Damasceno KA. Expression of VCAN and its receptors in canine mammary carcinomas with or without myoepithelial proliferation. Res Vet Sci. 2021;140:56\u201363.","journal-title":"Res Vet Sci"},{"key":"2423_CR28","doi-asserted-by":"crossref","unstructured":"Dos Reis DC, Damasceno KA, de Campos CB, Veloso ES, P\u00eagas GRA, Kraemer LR, Rodrigues MA, Mattos MS, Gomes DA, Campos PP, Ferreira E, Russo RC, Cassali GD. Versican and Tumor-Associated Macrophages promotes Tumor Progression and Metastasis in Canine and murine models of breast carcinoma. Front Oncol. 2019 Jul;3:9:577.","DOI":"10.3389\/fonc.2019.00577"},{"key":"2423_CR29","doi-asserted-by":"crossref","unstructured":"YeungTL, Leung CS, Wong KK, Samimi G, Thompson MS, Liu J, Zaid TM, Ghosh S, Birrer MJ, Mok SC. TGF-\u03b2 modulates ovarian cancer invasion by upregulating CAF-derived versican in the tumor microenvironment. Cancer Res 2013 Aug 15;73(16):5016\u201328.","DOI":"10.1158\/0008-5472.CAN-13-0023"},{"issue":"7225","key":"2423_CR30","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1038\/nature07623","volume":"457","author":"S Kim","year":"2009","unstructured":"Kim S, Takahashi H, Lin WW, et al. Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature. 2009;457(7225):102\u20136.","journal-title":"Nature"},{"key":"2423_CR31","doi-asserted-by":"crossref","unstructured":"Tanaka Y, Tateishi K, Nakatsuka T, Kudo Y, Takahashi R, Miyabayashi K, Yamamoto K, Asaoka Y, Ijichi H, Tateishi R, Shibahara J, Fukayama M, Ishizawa T, Hasegawa K, Kokudo N, Koike K. Sharpin promotes hepatocellular carcinoma progression via transactivation of Versican expression. Oncogenesis. 2016 Dec 12;5(12):e277.","DOI":"10.1038\/oncsis.2016.76"},{"key":"2423_CR32","doi-asserted-by":"crossref","unstructured":"Gupta N, Khan R, Kumar R, Kumar L, Sharma A. Versican and its associated molecules: potential diagnostic markers for multiple myeloma. Clin Chim Acta. 2015 Mar;10:442:119\u201324.","DOI":"10.1016\/j.cca.2015.01.012"}],"container-title":["Respiratory Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12931-023-02423-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12931-023-02423-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12931-023-02423-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T05:04:57Z","timestamp":1685509497000},"score":1,"resource":{"primary":{"URL":"https:\/\/respiratory-research.biomedcentral.com\/articles\/10.1186\/s12931-023-02423-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,31]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["2423"],"URL":"https:\/\/doi.org\/10.1186\/s12931-023-02423-4","relation":{},"ISSN":["1465-993X"],"issn-type":[{"value":"1465-993X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,31]]},"assertion":[{"value":"19 September 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 April 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 May 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The ethics committee of Tongji Hospital affiliated with Tongji University approved this study [(Tong) Lunxun-KYSB-2018-(087)]; Specimens were collected upon informed consent of either healthy volunteers or lung cancer cases.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"140"}}