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However, its specific role in clear cell renal cell carcinoma (ccRCC) remains unclear. This study aims to systematically investigate the expression patterns, clinical significance, prognostic value and functional role of STX16 in ccRCC. Bioinformatics analyses using TCGA, CTPAC, TIMER, and UALCAN databases evaluated STX16 expression, clinical correlations, prognosis, and immune infiltration. Functional enrichment, co-expression, and PPI analyses explored STX16-associated pathways. Single-cell sequencing elucidated tumor microenvironment heterogeneity. Laboratory validation included Western blot, immunohistochemistry, and functional assays with siRNA-mediated STX16 knockdown in ccRCC cell lines. STX16 was significantly upregulated at mRNA and protein levels in ccRCC tissues. High STX16 expression correlated with advanced tumor stages, poor overall survival (OS), and disease-specific survival (DSS). Multivariable Cox regression identified STX16 as an independent prognostic factor. STX16 influenced immune infiltration, particularly involving CD4\u2009+\u2009T cells, macrophages, and neutrophils, and was associated with immune pathways. Single-cell sequencing revealed heterogeneous STX16 expression across tumor microenvironment cell types. STX16 knockdown inhibited proliferation, migration, and invasion of ccRCC cell lines. STX16 is upregulated in ccRCC and acts as an independent prognostic factor associated with poor outcomes. Its role in promoting tumor progression and modulating immune infiltration highlights STX16 as a potential biomarker and therapeutic target in ccRCC.<\/jats:p>","DOI":"10.1038\/s41598-025-24921-9","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T11:20:37Z","timestamp":1763637637000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative analysis identifies STX16 as a prognostic and immune-associated biomarker in ccRCC"],"prefix":"10.1038","volume":"15","author":[{"given":"Yumeng","family":"Chai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Runze","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanshan","family":"Cui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongbao","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"issue":"12","key":"24921_CR1","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1001\/jama.2024.12848","volume":"24","author":"TL Rose","year":"2024","unstructured":"Rose, T. 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