Low CTDNEP1 Expression Predicts Poor Prognosis and Is Associated With Immune Modulation in Pancreatic Cancer

Abstract Background/Aim: Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy due to limited therapeutic options. Identifying novel genes that influence its progression is critical. This study aimed to investigate the role of CTDNEP1, a phosphatase-encoding gene, in PDAC using multi-omics data from The Cancer Genome Atlas (TCGA). Materials and Methods: We analyzed CTDNEP1 expression in PDAC using the TCGA and Pan-Cancer Atlas datasets. Kaplan-Meier survival analysis was performed to assess the association between CTDNEP1 expression and patient prognosis. Gene Ontology (GO) and KEGG pathway enrichment analyses were conducted to explore the biological processes linked to CTDNEP1 expression. Finally, we examined the relationship between CTDNEP1 expression and the tumor immune microenvironment using immune infiltration analysis. Results: CTDNEP1 expression was found to be significantly lower in PDAC tissues compared to normal tissues, especially in early-stage tumors. This downregulation was associated with mutations in key driver genes, including KRAS, CDKN2A, TP53, and SMAD4. Importantly, low CTDNEP1 expression correlated with significantly poorer patient prognosis, particularly in stage II PDAC. Functional enrichment analysis revealed that low CTDNEP1 expression is associated with macroautophagy, protein degradation, and immune/inflammatory pathways, while high expression is linked to mitochondrial function and metabolic activity. Furthermore, CTDNEP1 expression showed a positive correlation with immune cell infiltration. Conclusion: CTDNEP1 functions as a tumor suppressor in PDAC, influencing tumor progression, immune response, and patient survival. Future studies should investigate the detailed regulatory mechanisms of CTDNEP1 and explore its potential as a therapeutic target or biomarker for PDAC.