Prognostic and Immunomodulatory Roles of PAK6 in Colorectal Cancer Through Integrative Transcriptomic and Clinical...

Colorectal cancer (CRC) represents a major global health challenge, characterized by rising incidence and mortality rates, necessitating improved diagnostic and therapeutic approaches. This study aimed to elucidate the expression and functional role of PAK6, a protein linked to cancer progression, as a potential biomarker for CRC.

Utilizing comprehensive analyses of transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), we performed differential expression assessments, survival analyses, and functional enrichment studies.

Our findings demonstrate a significant upregulation of PAK6 in CRC tissues compared to adjacent normal tissues (p < 0.001), with a diagnostic AUC of 0.855, indicating its potential utility as a reliable biomarker for early detection. High PAK6 expression was significantly associated with aggressive clinicopathological features, including poor differentiation, residual tumor presence and reduced overall survival (HR = 1.72, p = 0.004). Functional enrichment analyses revealed PAK6's involvement in critical biological processes such as cell cycle regulation, alongside its correlation with immune infiltration, particularly NK and CD8⁺ T cells. Moreover, PAK6 expression positively correlated with chemokines involved in immune cell recruitment, suggesting its role in modulating the tumor immune microenvironment.

Our study underscores the significance of PAK6 as a diagnostic and prognostic biomarker in CRC, with the potential to inform targeted therapeutic strategies and enhance patient outcomes. Future research should focus on validating these findings in larger cohorts and exploring PAK6-targeted interventions to improve immunotherapeutic responses in CRC patients.