Differences in gene-expression in mCRC tissue samples with regard to tumor location and used chemotherapeutic substances: Data of the FIRE-1 study.

Abstract

562 Background: Colorectal cancer can be divided in different subgroups by their way of carcinogenesis. Clinically, right-sided (caecum, colon ascendens and transverse colon) and left-sided tumors (colon descendens, sigmoid and rectum) have different prognosis. The reasons behind the different prognosis remains unclear and can be found in both, anti-VEGF treated tumors and anti-EGFR treated tumors, with a more prominent effect for anti-EGFR treated patients. Until now, differences in efficacy of chemotherapeutic treatment between left-sided and right-sided colorectal cancer tumors have not been elucidated. Methods: 168 tumor samples of the FIRE-1 trial were investigated for RNA expression of the tumorous tissue. RNA was extracted of microdissected FFPE tissue and used for NanoString gene expression analysis. A total of 790 different RNAs were analyzed using the nCounter PanCancer Pathways Panel plus 20 RNA´s with key roles in the metabolism of substances commonly used in mCRC treatment. Using nSolver Software, normalization and quality control was done according to the manufacturer’s recommendations. Differences in expression between right- and left-sided tumors were calculated. P values were corrected using Benjamini-Yakutieli false discovery rate (FDR). Results: Data of 160 tumor samples passed QC and had sufficient data on location of the primary. Of the 790 tested RNA´s 70 showed significant differences in univariate analysis. Among those were EREG which has been reported to be of predictive value for anti-EGFR antibody treatment and ANGPT1 that has been reported to be of predictive value for anti-VEGF antibody treatment. Furthermore TS has been expressed differentially which has been reported to be predictive for the use of 5-FU. Conclusions: Patients with right-sided mCRC tumors have a worse prognosis when compared to left-sided tumors. Reasons for this are manifold. We are able to find significant differences in genes associated with 5-FU, anti-EGFR antibody, and anti-VEGF antibody treatment which may be able to explain some of the differences seen in clinical trials.