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

Histopathology. 2019 Oct;75(4):496-507. doi: 10.1111/his.13889. Epub 2019 Aug 2.


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.

Keywords: CXCL14; ICAM1; colorectal cancer; immune response; microsatellite instability; serrated.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology*
  • Adult
  • Aged
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology*
  • Female
  • Gene Expression Profiling
  • Humans
  • Male
  • Microsatellite Instability
  • Middle Aged
  • Transcriptome


  • Biomarkers, Tumor