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

## TL;DR

This study shows that PAK6 is overactive in colorectal cancer and linked to worse outcomes and immune changes, making it a potential biomarker for diagnosis and immunotherapy.

## Contribution

The study identifies PAK6 as a novel prognostic and immunomodulatory biomarker in colorectal cancer.

## Key findings

- PAK6 is significantly upregulated in tumor tissues and linked to aggressive disease features and poor survival.
- PAK6 correlates with immune cell infiltration and chemokine signaling in the tumor microenvironment.
- PAK6 shows a diagnostic AUC of 0.855, indicating its potential for early detection in colorectal cancer.

## Abstract

Colorectal cancer remains a major health challenge worldwide, highlighting the need for new diagnostic and prognostic biomarkers. In this study, we investigated the role of PAK6, a protein kinase, in colorectal cancer through integrative analysis of transcriptomic and clinical data. We found that PAK6 is significantly upregulated in tumor tissues and is associated with aggressive disease features and poorer patient survival. Importantly, PAK6 expression correlates with immune cell infiltration and chemokine signaling, suggesting its involvement in shaping the tumor immune microenvironment. Our findings indicate that PAK6 emerges as a candidate biomarker worthy of further investigation in colorectal cancer, with potential implications for guiding immunotherapy strategies in the future.

Background: 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. Methods: 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. Results: 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. Conclusions: 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