High COMP expression promotes tumor cell proliferation and migration of rectal cancer, contributing to unfavorable prognosis and suppressive immune microenvironment.

backgroundRectal cancer (RC) is a subtype of colorectal cancer, with high morbidity and mortality rates. Whereas, poor patient outcomes due to high aggressiveness urgently highlight the need for more effective markers and treatments. Hence, this work aims to explore novel pathogenic target in RC.

methodsThe RC expression data was derived from The Cancer Genome Atlas and Gene Expression Omnibus databases. The hub gene was identified using Weighted gene co-expression network analysis (WGCNA), differential expression analysis, protein-protein interaction (PPI) network, whose prognostic value was validated in public cohorts. Then, its impacts on RC cell viability, migration, invasion were determined by Cell Counting Kit-8 and Transwell assays.

resultsBy integrating data from WGCNA and differentially expressed genes, along with multiple protein-protein interaction (PPI) network algorithms, we identified seven key candidate genes. COMP was significantly highly expressed in RC samples, which was also successfully validated in additional cohorts and RC cell lines. In high COMP group, significantly higher infiltrating proportion of M2 macrophages was observed. Along with tumor stage progressed, COMP expression was up-regulated accordingly, implying its tumor promoting roles. Consistent with this, silencing COMP in RC cells significantly inhibited cell viability, migration, and invasion in vitro. In high COMP expression group, patients exhibited inferior prognosis independently of other risk factors, and 18 pathways like TGF-β signaling pathway were significantly enriched.

conclusionCollectively, significant higher COMP expression was noticed in public RC cohorts and RC cells, and si-COMP obviously inhibited the cell viability, migration, and invasion, implying its pathogenic role in RC.