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Vascular endothelial growth factor-D (VEGF-D) is an important biomarker for LAM.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>This study cohort comprised 631 LAM patients and investigated the correlations between serum VEGF-D levels and clinical manifestations of LAM. The median serum level of VEGF-D was 1452pg\/ml (820.0-2659pg\/ml) among the study population. Patients with highly-elevated VEGF-D levels exhibited younger age, lower BMI, and a higher prevalence of tuberous sclerosis complex (TSC). Elevated VEGF-D levels were associated with a lower prevalence of pneumothorax and angiomyolipomas (AMLs), and a higher risk for retroperitoneal lymphangioleiomyomas and chylous effusion. Elevated VEGF-D levels were associated with increased High-Resolution Computed Tomography (HRCT) LAM grading, reduced forced expiratory volume in one second (FEV<jats:sub>1<\/jats:sub>) and diffusion capacity for carbon monoxide (DLco), and decreased arterial oxygen partial pressure. Multiple logistic regression analysis identified age, TSC, AMLs, retroperitoneal lymphangioleiomyomas, chylous effusion, and HRCT grade as independent risk factors for elevated VEGF-D levels. As a diagnostic biomarker for LAM, adding VEGF-D in the diagnostic algorithm enabled the diagnosis of LAM without lung biopsy in 83.5% patients with LAM.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The findings highlighted the pivotal role of serum VEGF-D in LAM pathophysiology and underscore that age, TSC, retroperitoneal LAM, chylous effusion, AMLs, and high HRCT grade were independent risk factors for increased VEGF-D levels. VEGF-D is a valuable biomarker in evaluation of LAM and improve the efficiency of diagnostic algorithm.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13023-025-03802-4","type":"journal-article","created":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T18:11:14Z","timestamp":1748283074000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Associations of VEGF-D levels with clinical manifestations in lymphangioleiomyomatosis: a cross-sectional analysis of 631 cases"],"prefix":"10.1186","volume":"20","author":[{"given":"Luning","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanghang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongsheng","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaoyan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danjing","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yani","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengyue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenshuai","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junya","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinrong","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuzhen","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanli","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao-Ting","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlun","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7662-531X","authenticated-orcid":false,"given":"Kai-Feng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,26]]},"reference":[{"key":"3802_CR1","doi-asserted-by":"publisher","first-page":"1289388","DOI":"10.3389\/fphys.2023.1289388","volume":"14","author":"M Soleimani","year":"2023","unstructured":"Soleimani M. 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The LAM-CHINA registry research was approved by the ethical committee of the PUMCH (JS1323).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All patients signed the informed consent.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"255"}}