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

Abstract:

AIMS:To discern the differences in expression profiling of two histological subtypes of colorectal carcinoma (CRC) arising from the serrated route (serrated adenocarcinoma (SAC) and CRC showing histological and molecular features of a high level of microsatellite instability (hmMSI-H) both sharing common features (female gender, right-sided location, mucinous histology, and altered CpG methylation), but dramatically differing in terms of prognosis, development of an immune response, and treatment options. METHODS AND RESULTS:Molecular signatures of SAC and hmMSI-H were obtained by the use of transcriptomic arrays; quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC) were used to validate differentially expressed genes. An over-representation of innate immunity functions (granulomonocytic recruitment, chemokine production, Toll-like receptor signalling, and antigen processing and presentation) was obtained from this comparison, and intercellular cell adhesion molecule-1 (ICAM1) was more highly expressed in hmMSI-H, whereas two genes [those encoding calcitonin gene-related peptide-receptor component protein and C-X-C motif chemokine ligand 14 (CXCL14)] were more highly expressed in SAC. These array results were subsequently validated by qPCR, and by IHC for CXCL14 and ICAM1. Information retrieved from public databanks confirmed our findings. CONCLUSIONS:Our findings highlight specific functions and genes that 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.

journal_name

Histopathology

journal_title

Histopathology

authors

García-Solano J,Turpin-Sevilla MDC,García-García F,Carbonell-Muñoz R,Torres-Moreno D,Conesa A,Conesa-Zamora P

doi

10.1111/his.13889

subject

Has Abstract

pub_date

2019-10-01 00:00:00

pages

496-507

issue

4

eissn

0309-0167

issn

1365-2559

journal_volume

75

pub_type

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