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ADAM15 stands out as a pivotal mediator in multiple tumor types, responding to immune checkpoint inhibitors (ICI) significantly. By promoting pro\u2010angiogenic genes, potentiating integrin binding as well as modulating the inflammatory response, ADAM15 orchestrates cellular adhesion and migration, thereby fostering tumor progression. Despite these compelling insights, the intricate roles of ADAM15 in prediction, immune modulation, and therapeutic targeting among malignant disorders remain largely unexplored. To decipher the pan\u2010cancer landscape of ADAM15, we integrated data from multiple databases. Immunohistochemical profiles of ADAM15 were retrieved from the human protein atlas (HPA) database. Furthermore, the tumor immune estimation resource (TIMER) and the ESTIMATE (Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data) algorithm were harnessed to dissect the immune infiltration patterns and immune checkpoint genes associated with ADAM15. The tumor immune single\u2010sample gene set enrichment analysis (TISMO) was employed to explore the impact of ADAM15 on the tumor immune microenvironment. Additionally, drug sensitivity analysis and subsequent molecular docking studies were conducted to identify potential therapeutic compounds targeting ADAM15. These findings were rigorously validated through reverse transcription\u2010polymerase chain reaction (RT\u2010PCR), western blotting (WB), and immunohistochemistry (IHC) by cell lines and clinical samples from hepatocellular carcinoma (HCC) as well as colon adenocarcinoma (COAD). Our comprehensive analysis revealed that ADAM15 is markedly upregulated in diverse cancer types. IHC, WB, and RT\u2010PCR assays of HCC and COAD confirmed these findings. Notably, elevated ADAM15 correlates with adverse prognosis in pan\u2010cancer, positioning it as a promising novel biomarker. Drug sensitivity profiling unveiled a positive and statistically significant association between ADAM15 and AZD\u20108055 and Nitazoxanide, whereas a negative correlation was observed with Oxaliplatin and Ponatinib. These findings were further corroborated by molecular docking simulations, highlighting the potential of these compounds as therapeutic targets for ADAM15\u2010driven cancers. Our study underscores the multifaceted role of ADAM15 in cancer progression, immune evasion, and response to therapy. By elucidating the intricate interplay between ADAM15 and the tumor microenvironment (TME), we have identified novel diagnostic biomarkers and potential therapeutic avenues.<\/jats:p>","DOI":"10.1002\/iub.70086","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T07:03:07Z","timestamp":1770102187000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>ADAM15<\/scp>\n                    Is a Potential Biomarker for Pan\u2010Cancer Prognosis and Immunotherapy: Validation in\n                    <scp>HCC<\/scp>\n                    and\n                    <scp>COAD<\/scp>"],"prefix":"10.1002","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4746-0971","authenticated-orcid":false,"given":"Wenjia","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Shanghai East Hospital, School of Medicine Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2019e","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wencong","family":"Ma","sequence":"additional","affiliation":[{"name":"Institute of Hepatobiliary and Pancreatic Surgery, Department of Hepatobiliary and Pancreatic Surgery, Shanghai East Hospital, School of Medicine Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lieying","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Shanghai East Hospital, School of Medicine Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingdi","family":"Chen","sequence":"additional","affiliation":[{"name":"The Institute for Biomedical Engineering and Nano Science, School of Medicine Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghan","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Hepatobiliary and Pancreatic Surgery, Department of Hepatobiliary and Pancreatic Surgery, Shanghai East Hospital, School of Medicine Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"98","article-title":"The Distribution of Secondary Growths in Cancer of the Breast. 1889","volume":"8","author":"Paget S.","year":"1989","journal-title":"Cancer Metastasis Reviews"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21820"},{"key":"e_1_2_10_4_1","volume-title":"World Health Statistics 2023: Monitoring Health for the SDGs, Sustainable Development Goals","author":"Organization 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