Abstract B38: Early-onset colorectal cancer gene-expression profiling: An analysis of TCGA data

Abstract

Background: Colorectal cancer (CRC) is the 2nd and 1st leading cause of cancer-related deaths in men and women in the US and Puerto Rico, respectively. CRC is associated with aging; however, the incidence of sporadic, early-onset (<50 years old) CRC patients is on the rise despite a decrease in the incidence of late-onset CRC (≥65 years old). Early-onset CRC represents a clinically distinct form of CRC often associated with poor prognosis. The aim of this study was to compare early-onset CRC tumor RNAseq gene expression profiles to late-onset CRC profiles available through The Cancer Genome Atlas (TCGA) in order to gain insight into the molecular changes leading to early-onset CRC. Method: RNAseq data from individuals <50 and ≥ 65 (n=313) years old with colon adenocarcinoma was downloaded from the TCGA Data Portal (https://tcga-data.nci.nih.gov/tcga/). A comparison between RNAseq data from individuals <50 years and >65 years was performed using edgeR (https://bioconductor.org/packages/release/ bioc/html/edgeR.htm). Only genes with at least two counts per million (CPM) in at least 60 samples were further analyzed. False discovery rate (FDR) was set to less than 5% in the analysis. Results: A total of 373 individuals with CRC were available using TCGA data: 60 with early onset (<50 years) and 313 with late onset (≥ 65 years old). A total of 14,280 genes were analyzed. Differential gene expression analysis showed 1,574 differentially upregulated and 1,200 downregulated gene expression profiles when comparing early-onset versus late-onset tumor profiles. Significantly overexpressed genes in early-onset CRC include mucin 5b, a major gel-forming mucin in mucus (log fold change=11.03; p value=1.10E-05), and resistin like beta, associated with Barrett's esophagus/esophageal adenocarcinoma and involved in IL4-mediated signaling events (log fold change=7.65; p value=0.001). Conclusion: This is the first characterization of gene expression profiles in early-onset CRC patients included in the TCGA database. The observed differences in gene expression have to be further analyzed in order to gain insight into the molecular pathways leading to sporadic early-onset CRC. Furthermore, a more comprehensive understanding of the biology of sporadic early-onset CRC is needed in order to directly address this emerging public health problem and to subsequently shift current clinical practices for young patients falling outside of current screening guidelines across the cancer continuum, from prevention strategies to screening and/or treatment. Citation Format: Maria Gonzalez-Pons, Luis Vazquez, Marcia Cruz-Correa. Early-onset colorectal cancer gene-expression profiling: An analysis of TCGA data. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr B38.