Transcriptomic validation and clinical translation of CCDC78 as a prognostic biomarker in colorectal cancer.

Abstract

This study investigates CCDC78 as a potential prognostic biomarker in colorectal cancer (CRC), incorporating both clinical correlation and functional validation. Analysis of 135 paired tumor and adjacent tissues revealed significantly elevated CCDC78 expression in tumor tissues (P<0.001), and higher expression levels were associated with markedly lower 5-year survival rates (P=0.001). Time-dependent ROC curves demonstrated robust prognostic performance at 12, 36, and 60 months (AUCs of 0.85, 0.84, and 0.82, respectively). In vitro assays showed that CCDC78 overexpression significantly enhanced cell proliferation, migration, and invasion (P<0.05), whereas siRNA-mediated knockdown suppressed these phenotypes and increased apoptosis (P<0.01). Cox regression analyses identified CCDC78 as an independent prognostic factor (P=0.02). Notably, despite similar baseline expression across CRC cell lines, SW480 cells were more sensitive to knockdown, while HCT116 cells more strongly recapitulated the overexpression phenotype. TCGA pan-cancer analysis showed upregulated CCDC78 in various tumors, including CRC, adrenocortical carcinoma (ACC), bladder cancer (BLCA), and kidney renal clear cell carcinoma (KIRC), reinforcing its broad oncogenic relevance. Correlation analyses linked high CCDC78 expression to older age, poor tumor differentiation, advanced TNM stage, lymph node metastasis, and distant metastasis. Immune profiling revealed negative associations with 11 immune cell types but a positive correlation with NK CD56 bright cells. Gene set enrichment analysis (GSEA) implicated CCDC78 in interferon-JAK-STAT, RIG-I/NFκB, and WNT signaling pathways. Altogether, these findings suggest that CCDC78 promotes CRC progression through enhancing tumor cell aggressiveness and modulating the immune microenvironment, underscoring its potential as a prognostic biomarker and therapeutic target.