Combining Gene Expression Data with GWAS Highlights the Causal Gene CCDC25 as a Biomarker for a Favorable Prognosis in Colorectal Cancer

Abstract

Background. Coiled-coil domain containing 25 (CCDC25) is a receptor for neutrophil extracellular trap (NET) DNA and is involved in various cancers, including CRC. This study aimed to investigate the regulatory role of CCDC25 in CRC using GWAS data, eQTL, transcriptomic profiles, and clinical information of CRC patients. Methods. From open-source databases, GWAS summary data, eQTL expression profiles, and transcriptomic profiles, as well as clinical information were collected for CRC patients. Mendelian randomization (MR) was used to investigate the causal relationship between CCDC25 and CRC risk. The expression of CCDC25 and its associated differentially expressed genes (DEGs) were identified. We explored the relationship between CCDC25 expression and survival, biological functions, immune cell infiltration, immune checkpoint expression, and response to immunotherapy. Results. High CCDC25 expression reduces the risk of CRC. CCDC25 is downregulated in various cancers, particularly in CRC tumor tissues compared to normal tissues. Metabolic pathways are enriched in groups with high CCDC25 expression, while cancer-related pathways are enriched in groups with low CCDC25 expression. High CCDC25 expression is also associated with increased infiltration of resting memory CD4+ T cells, elevated levels of most immune checkpoints, and an enhanced response to anti-PD1 therapy. In addition, 95 DEGs were identified between high-CCDC25 and low-CCDC25 groups, and eight genes (FDFT1, ASAH1, ADAM9, CXCL14, SERPINA1, NAT1, EREG, and GSR) were identified as prognostic genes. Conclusion. CDC25 might serve as a candidate diagnostic and prognostic marker for CRC patients.