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
Histopathologyjournal_title
Histopathologyauthors
García-Solano J,Turpin-Sevilla MDC,García-García F,Carbonell-Muñoz R,Torres-Moreno D,Conesa A,Conesa-Zamora Pdoi
10.1111/his.13889subject
Has Abstractpub_date
2019-10-01 00:00:00pages
496-507issue
4eissn
0309-0167issn
1365-2559journal_volume
75pub_type
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