Differences in gene expression profiling and biomarkers between histological colorectal carcinoma subsets from the serrated pathway
Por:
Garcia-Solano, J, Turpin-Sevilla, M, Garcia-Garcia, F, Carbonell-Munoz, R, Torres-Moreno, D, Conesa, A and Conesa-Zamora, P
Publicada:
1 oct 2019
Resumen:
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.
Filiaciones:
Garcia-Solano, J:
Santa Lucia Gen Hosp, Dept Pathol, Cartagena, Spain
Catholic Univ Murcia, Fac Ciencias Salud Cathol, Murcia, Spain
Inst Murciano Invest Biosanitarias, Murcia, Spain
Turpin-Sevilla, M:
Francisco Vitoria Univ, Madrid, Spain
:
Ctr Invest Principe Felipe, Bioinformat & Biostat Unit, Valencia, Spain
Carbonell-Munoz, R:
Santa Lucia Gen Hosp, Dept Pathol, Cartagena, Spain
Santa Lucia Gen Univ Hosp, Dept Clin Anal, Cartagena, Spain
Torres-Moreno, D:
Santa Lucia Gen Hosp, Dept Pathol, Cartagena, Spain
Inst Murciano Invest Biosanitarias, Murcia, Spain
Conesa, A:
Ctr Invest Principe Felipe, Bioinformat & Biostat Unit, Valencia, Spain
Conesa-Zamora, P:
Catholic Univ Murcia, Fac Ciencias Salud Cathol, Murcia, Spain
Inst Murciano Invest Biosanitarias, Murcia, Spain
Santa Lucia Gen Univ Hosp, Dept Clin Anal, Cartagena, Spain
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