Abstract 141: Gene expression profile differences between early- and late-onset colorectal adenocarcinoma

Abstract

Abstract Introduction: Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer related deaths in the US. The overall incidence of CRC in the US has decreased over the past three decades, yet recent literature indicates increase in incidence among individuals younger than 50. These early-onset CRC tumors (EO) tend to be more aggressive and advanced at initial diagnosis. As the etiology of EO CRC is not understood yet, the aim of this study was to elucidate gene expression profiling in EO CRC and show its molecular uniqueness compared to late-onset (LO) CRC. Methods: Two cohorts of patients with sporadic EO CRC (age under 50) and LO CRC (age over 65) tumors were identified. Tumors and their matching non-involved tissue samples with equal representation of colon and rectal neoplasms from twelve EO patients and twelve LO patients were obtained. Patients with Lynch syndrome, familial adenomatous polyposis and inflammatory bowel disease were excluded. De-paraffinized tissues were macro-dissected from FFPE sections, RNA isolated and used for nanoString nCounter PanCancer Pathways Panel gene expression analysis to quantify transcript levels of 770 genes representing 13 canonical cancer pathways. Statistical analysis was performed using the Gene Expression R-script module within the nCounter software v2.6. A gene was considered to be above background if the average count for the target gene was greater than the average counts for the eight negative control genes and if the P value of the t-test was less than 0.05. Results: We analyzed a total of twenty four tumor samples, six EO and six LO colon tumors and six EO and six LO rectal tumors. Their expression profiles were then compared to their matching non-involved tissues in order to identify genes that are unique to colon and rectal neoplasm, respectively. Out of 770 PanCancer Panel pathway genes assayed, 98 genes were uniquely expressed in EO colon tumors with 73 genes being up- and 25 down-regulated with a fold change higher than two. 77 genes were uniquely expressed in EO rectal tumors, with 57 of them up-regulated and 20 down-regulated. Further statistical analysis revealed that, from 265 genes differentially expressed specifically in EO colon tumors, changes in expression of 147 genes were statistically significant (p<0.05). Similarly, from 275 genes differentially expressed in EO rectal tumors, 82 showed statistically significant alterations in expression. Conclusions: Results of this study suggest EO CRC as a distinct molecular subtype which is characterized by unique molecular events compared to LO disease. Further studies using larger cohorts of patients are needed to validate these findings. Such studies might offer the possibilities of coming up with novel molecular markers to enhance newer, faster and noninvasive detection modalities for young patients with CRC tumors. Citation Format: Valentine N. Nfonsam, Jana Jandova. Gene expression profile differences between early- and late-onset colorectal adenocarcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 141.