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

• Published in: Histopathology 2019-10, Vol.75 (4), p.496-507
• Main Authors: García‐Solano, José, Turpin‐Sevilla, María del Carmen, García‐García, Francisco, Carbonell‐Muñoz, Rosa, Torres‐Moreno, Daniel, Conesa, Ana, Conesa‐Zamora, Pablo
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adult; Aged; Antigen presentation; Antigen processing; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Calcitonin; Cell adhesion & migration; Cell adhesion molecules; Chemokines; colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; CpG islands; CXCL14; DNA methylation; Female; Gene expression; Gene Expression Profiling; Humans; ICAM1; Immune response; Immunohistochemistry; Information processing; Innate immunity; Intercellular adhesion molecule 1; Male; Microsatellite Instability; Middle Aged; Polymerase chain reaction; serrated; Signal transduction; Toll-like receptors; Transcriptome
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/his.13889

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.