Differences in expression profiling and biomarkers between histological colorectal carcinomas subsets from the serrated pathway.

Abstract

Histological subtypes of colorectal carcinomas (CRCs) arising from the serrated route, such as serrated adenocarcinoma (SAC) and CRC showing histological and molecular features of microsatellite instability (hmMSI-H), share common features (female gender, right-sided location, mucinous histology and altered CpG methylation) but dramatically differ in terms of prognosis, development of immune response and treatment options. Despite this, to date no expression profiling comparison has been carried out for finding out functions and molecules responsible for such differences.

METHODS AND RESULTS: Molecular signatures of SAC and hmMSI-H were obtained by transcriptomic array; qPCR and immunohistochemistry (IHC) were used to validate differentially expressed genes. An over-representation of innate immunity functions (granulomonocytic recruitment, chemokine production, TLR signaling, antigen processing and presentation) were obtained from this comparison and ICAM1 was more expressed in hmMSI-H whereas two genes (CRCP and CXCL14) were more expressed in SAC. These array results were subsequently validated by qPCR, and CXCL14 and ICAM1 by IHC. Information retrieved from public databanks confirmed our findings.

CONCLUSIONS: Our findings highlight specific functions and genes which provide a better understanding of the role of the immune response in the serrated pathological route and may be of help in identifying actionable molecules. This article is protected by copyright. All rights reserved.