Differential Expression of PEG10 Contributes to Aggressive Disease in Early Versus Late-Onset Colorectal Cancer

BACKGROUND: Colorectal cancer is a leading cause of cancer-related death. Early onset colorectal cancer (age <= 45 y) is increasing and associated with advanced disease. Although distinct molecular subtypes of colorectal cancer have been characterized, it is unclear whether age-related molecular differences exist. OBJECTIVE: We sought to identify differences in gene expression between early and late-onset (age >= 65 y) colorectal cancer. DESIGN: We performed a review of our institution's colorectal cancer registry and identified patients with colorectal cancer with tissue specimens available for analysis. We used the Cancer Genome Atlas to initially identify differences in gene expression between early and late-onset colorectal cancer. In vitro experiments were performed on 2 colorectal cancer cell lines. SETTINGS: The study was conducted at a tertiary medical center. PATIENTS: Patients with early onset (n = 28) or late onset (age > 65 y; n = 38) at time of diagnosis were included. MAIN OUTCOME MEASURES: The primary outcome was differential gene expression in patients with early versus late-onset colorectal cancer. The secondary outcome was patient mortality. RESULTS: Seven genes had increased expression in younger patients using The Cancer Genome Atlas. Only PEG10 was sufficiently expressed with quantitative polymerase chain reaction and had increased expression in our early onset group. Multivariable linear regression analysis identified age as a significant independent predictor of increased PEG10 expression. Outcomes data from The Cancer Genome Atlas suggests that PEG10 is associated with poor overall survival. In vitro studies in HCT-116 and HT-29 cell lines showed that PEG10 contributes to cellular proliferation and invasion in colorectal cancer. LIMITATIONS: Tissue samples were from formalin-fixed, paraffin-embedded sections. Many patients did not have mutational status for review. CONCLUSIONS: PEG10 is differentially expressed in early onset colorectal cancer and may functionally contribute to tumor cell proliferation and invasion. An increase in PEG10 expression correlates with decreased overall survival. See Video Abstract at http://links.lww.com/DCR/B343.