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Among the histological subtypes of lung cancer, lung adenocarcinoma (LUAD) predominates and is frequently diagnosed at an advanced stage, contributing to its dismal 5-year survival rate and posing a significant threat to patient survival. In this work, the expression, prognosis and diagnostic of CLDNs in pan-cancer were analyzed using bioinformatics. In particular, the relationship between claudin12 (CLDN12) and the expression, prognosis and clinical stage in LUAD was paid attention to, and the diagnostic efficiency of CLDN12 was evaluated by receiver operator characteristic curve. The PPI network was constructed using STRING database, followed by Cytoscape-assisted hub gene identification. Functional enrichment analyses (GO and KEGG) were conducted to elucidate potential signaling pathways linked to CLDN12. These results showed that CLDNs were differentially expressed in pan-cancer, and were valuable for the prognosis and diagnosis of tumors. Specifically, CLDN12 was significantly upregulated in LUAD, correlating with advanced tumor stage, lymph nodes metastasis, and poor survival outcomes. In vitro functional assays revealed that CLDN12 knockdown suppressed LUAD cell proliferation, migration, and invasion while promoting cell apoptosis. In summary, CLDN12 may serve as a promising biomarker for LUAD detection and a potential therapeutic target.<\/jats:p>","DOI":"10.1038\/s41598-025-28317-7","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T13:43:37Z","timestamp":1767015817000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The claudin family characteristics in pan-cancer and the role of claudin12 in the malignant progression of lung adenocarcinoma"],"prefix":"10.1038","volume":"15","author":[{"given":"Pei","family":"Gao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxin","family":"Bian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yixuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weixin","family":"Jing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"issue":"3","key":"28317_CR1","first-page":"229","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray, F. et al. 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