# Integrative analysis identifies STX16 as a prognostic and immune-associated biomarker in ccRCC

## TL;DR

This study finds that STX16 is upregulated in kidney cancer and linked to worse outcomes and immune changes, suggesting it could be a new biomarker or treatment target.

## Contribution

The study identifies STX16 as a novel prognostic and immune-related biomarker in clear cell renal cell carcinoma (ccRCC).

## Key findings

- High STX16 expression correlates with advanced tumor stages and poor survival in ccRCC patients.
- STX16 knockdown reduces ccRCC cell proliferation, migration, and invasion.
- STX16 is associated with immune infiltration by CD4+ T cells, macrophages, and neutrophils.

## Abstract

STX16 has been studied in various cancers, where it is suggested to regulate tumor cell proliferation, migration, and invasion by affecting vesicle trafficking and signal transduction pathways. 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 + T 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.

The online version contains supplementary material available at 10.1038/s41598-025-24921-9.