Cartilage Oligomeric Matrix Protein, COMP may be a Better Prognostic Marker Than CEACAM5 and Correlates With Colon Cancer Molecular Subtypes, Tumor Aggressiveness and Overall Survival

Abstract

New tumor biomarkers are needed to improve the management of colon cancer (CC), the second leading cause of cancer-related deaths in the United States. Carcinoembryonic Antigen (CEA), the translated protein of carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) gene, is used as a biomarker for CC.Cartilage Oligomeric Matrix Protein (COMP)is overexpressed in CC compared to normal colon tissues. This study aims to evaluate the expression ofCOMPby disease stage, consensus molecular subtype (CMS), its impact on disease outcomes, and comparison to CEACAM5. RNA-seq data from 456 CC The Cancer Genome Atlas samples and 41 matching control samples were analyzed forCOMPexpression andCEACAM5expression. We stratified tumor samples by stage (I-IV), subtype (CMS1-CMS4), tumor location, and Kirsten RAt Sarcoma(KRAS)mutant status and three quartiles were established based on COMPexpression. Kaplan Meier survival outcomes were evaluated. COMPexpression was significantly higher in tumor samples, with elevation of expression occurring in stage I and significantly increasing in stage IV. IncreasedCOMPexpression occurs in CMS4 with relatively low expression in CMS3. No significant expression difference was attributed to tumor location and KRAS mutant status. Compared to CEACAM5, COMP was a stronger molecular marker across stages and subtypes. CMS4 was associated with the highCOMPexpression, and higher levels ofCOMPwere associated with poorer overall survival, disease-specific survival, and tumor progression-free intervals. CMS2 and 3 were associated with low expression and better survival. COMP is a potential molecular biomarker for CC and may be superior to CEA as an indicator of CC.