The Role And Functional Mechanism Of COMP In Colon Cancer

Objective: Cartilage oligomeric matrix protein(COMP)is a member of the thrombospondin gene family,and recent studies have determined that COMP plays a vital role in carcinogenesis.We sought to clarify the expression patterns and clinical significance of COMP in colon cancer.Methods: We investigated gene expression data from The Cancer Genome Atlas(TCGA)dataset and analyzed the correlations between COMP m RNA expression levels and clinical parameters.Tissue microarrays(TMA)containing paired samples from 253 patients with colon cancer were subjected to immunostaining.COMP levels in serum of colon cancer patients and healthy donors were measured with a new sandwich ELISA.We established COMP-knockout Lo Vo cells using the CRISPR/Cas9 system and COMP-overexpressing SW1116 cells using lentiviral vectors.We then detected the effects of COMP knockout and overexpression on colon cancer cells using Cell Counting Kit-8(CCK8),colony formation,cell migration,cell invasion and tumorigenesis assays in nude mice.In addition,we explored the pathway that contributes to the development of the malignant phenotype.Results: The analysis of TCGA dataset and the results of the TMA suggested that COMP expression levels were significantly higher in cancer tissues than in adjacent normal tissues.Moreover,COMP expression was significantly correlated with the unfavorable clinical characteristics.COMP served as an independent prognostic indicator for poor clinical outcome in patients with colon cancer.COMP levels in the sera of preoperative patients with colon cancer were much higher than those in healthy donors and were significantly reduced after colectomy.Colon cancer cells without COMP were defective with respect to the ability to proliferate,migrate,and invade,the ability to resist5-Fluorouracil-induced apoptosis,and the growth of xenograft tumors in mice.Contrasting results were observed after COMP was overexpressed in SW1116 cells.The activation of phosphatidylinositol 3-kinase(PI3K)/Akt/mammalian target of rapamycin(m TOR)/70-k Da ribosomal protein S6 kinase(p70S6K)pathway and the promotion of the epithelial-mesenchymal transition(EMT)in colon cancer by COMP partially contributed to the development of the malignant phenotype.Conclusions: Given its importance in colon carcinogenesis and cancer progression,COMP may be useful as a novel prognostic indicator in and biomarker for colon cancer.Moreover,COMP may be a potential target in the therapeutic manipulation of colon cancer.