GJB5 expression in pancreatic adenocarcinoma: prognostic significance and therapeutic implications

Gap junction protein 5 (GJB5) has been associated with tumorigenesis; however, its exact role in pancreatic adenocarcinoma (PAAD) remains unclear. This study investigates GJB5's expression, its functional roles in tumor progression, and its prognostic significance in PAAD.

This study used multiple bioinformatics tools, including Tissue Infiltrating Microenvironment Estimation Resource 2, University of Alabama at Birmingham Cancer, Tumor Immune System Interaction Database, Gene Expression Profiling Interactive Analysis 2, and cBioPortal. These tools were used to analyze GJB5 expression, its correlation with immune cell infiltration, and its potential as a prognostic biomarker in PAAD. Functional assays, including cell counting kit-8, colony formation, wound healing, and transwell assays, were performed to investigate the impact of GJB5 on PAAD tumor cell behaviors, including proliferation, migration, and invasion. Additionally, pathways associated with GJB5 and its interactions with the tumor microenvironment were explored.

GJB5 was significantly overexpressed in PAAD tissues compared to adjacent normal tissues. Promoter hypomethylation, rather than somatic mutation, was identified as the primary mechanism driving GJB5 upregulation. Survival analysis and Cox regression models indicated that upregulated GJB5 expression is an independent prognostic factor for poor survival in patients with PAAD. Furthermore, GJB5 expression was positively correlated with immune cell infiltration in the PAAD microenvironment. Functional assays exhibited that silencing GJB5 reduced cell proliferation, migration, and invasion in PAAD cell lines.

GJB5 is a significant prognostic biomarker for PAAD and a potential therapeutic target for reversing tumor progression, providing novel strategies for PAAD treatment.