Integrated bioinformatics and experimental validation identify CCDC78 as a prognostic biomarker in colon...

Colon adenocarcinoma (COAD) is the third most common malignancy globally, with recurrence and metastasis driving cancer-related mortality. Improved biomarkers and preventive strategies are urgently needed. Coiled-coil domain containing 78 (CCDC78) is believed to be linked with tumor progression, yet its specific role in COAD remains largely uncharacterized. This study elucidates the prognostic and functional roles of CCDC78 in COAD through integrated bioinformatics and experimental validation. Multi-omics data, The Cancer Genome Atlas (TCGA)-COAD cohort and GSE39582 database, revealed CCDC78 overexpression correlated with advanced TNM stages (p < 0.001), reduced drug sensitivity, and poorer overall survival (HR = 1.84, 95% CI: 1.23-2.74). Cox regression identified CCDC78 as an independent prognostic factor, integrated into a validated nomogram. Functional enrichment linked CCDC78 to cell cycle regulation, with GSCA analysis showing copy number variation (CNV)-driven pathway activation. Experimental validation demonstrated CCDC78 knockdown suppressed proliferation and migration in COAD cells. Mechanistically, CCDC78 potentially downregulates CDKN1A-CDK4 and activates E2F1 signaling. These findings establish CCDC78 as both a prognostic biomarker and therapeutic target. The study bridges computational predictions with functional evidence, proposing CCDC78 as a novel oncogenic driver in COAD through cell cycle dysregulation. Future investigations will employ in vivo models to delineate its molecular mechanisms.