Increasing Incidence of Colon Cancer in the Young: Assessing the Tumor Biology

Abstract

The overall incidence of colon cancer (CC) is decreasing, but with increasing early-onset colon cancer (EOCC < 50 years old). Our recent study revealed unique overexpression of cartilage oligomeric matrix protein (COMP) in EOCC and its association with aggressiveness. The aim of this study was to assess CC biology, especially in the young, by evaluating the role of COMP in CC carcinogenesis and cancer progression, detecting COMP in serum and its association with disease stage. Cancer and matching noninvolved tissue blocks from 12 sporadic EOCC and late-onset colon cancer (LOCC) patients of 4 disease stages were obtained from pathology archives. Ribonucleic acid expression profiling of 770 cancer-related genes using nCounter platform was performed. The COMP levels from 16 EOCC and LOCC serum samples were measured by ELISA. Carcinoembryonic antigen levels from these 16 samples were taken at the time of diagnosis. Transwell assay was performed to elucidate the role of COMP in motility and metastases. Expression profiling revealed increased COMP levels in higher disease stage. There was 7-fold higher COMP expression (p ≤ 0.05) in stage III compare to stage I and its coexpression with GAS1, VEGFC, MAP3K8, SFRP1, and PRKACA. Higher COMP expression was seen in stage II compared with stage I (p= 0.07) and its coexpression withTLR2, IL8, RIN1, IRAK3, and CACNA2D2, and COMP was detectable in serum and showed significantly higher levels in EOCC compared with LOCC. Similar correlation was seen with CEA levels, but the difference was not significant. Transwell assay revealed significantly increased motility of HT-29 cells after treatment with recombinant COMP. These findings suggest different tumor biology between EOCC and LOCC. Cartilage oligomeric matrix protein plays a significant role in CC carcinogenesis and has potential as biomarker for CC, especially aggressive EOCC.