Chitinase domain containing 1 increase is associated with low survival rate and M0 macrophages infiltrates in colorectal cancer patients

Pathol Res Pract. 2022 Sep:237:154038. doi: 10.1016/j.prp.2022.154038. Epub 2022 Jul 22.

Abstract

Colorectal cancer (CRC) is one of the most common cancers in the world. Here, we undertook an analysis of microarray datasets consisting of colon biopsies of healthy subjects and of patients affected by CRC, in order to analyze the expression levels of Chitinase domain-containing protein 1 (CHID1) and to correlate them with the clinical data available in the datasets. Analysis of expression levels showed a significant increase of CHID1 in CRC biopsies compared to the mucosa of healthy subjects. Patients' stratification by TNM staging revealed significant increases in CHID1 expression levels as the disease progressed. Furthermore, we found that mutated BRAF patients exhibit higher levels of CHID1 expression. Patients with a poor surviving prognosis at 5 years expressed high levels of CHID1 compared to wild-type. The histochemical analysis carried out by the Human Protein Atlas web tool documented moderate to strong-intensity staining detection of CHID1 protein in CRC biopsies. Furthermore, CRC patients were selected and clustered into two groups, high and low CHID1 expression levels (HCEL and LCEL). We obtained two signatures, the genes significant positive (GSPC-CHID1) and negative (GSNC-CHID1) correlated to CHID1 expression levels. The genomic deconvolution analysis between the GSPC-CHID1, GSNC-CHID1, and 17 cell immunological signatures, highlighted the potential infiltration of Macrophages M0 in HCEL patients, and potential infiltration of Macrophages M1 cells in LCEL patients. In addition, the signature GSPC-CHID1 expressed unfavorable genes to the CRC patient's survival. Mirror results were obtained for the GSNC-CHID1 signature. From the outcome of our investigation, it is possible to conclude that HCEL are associated with an unfavorable prognosis for CRC patients.

Keywords: Bioinformatics; Chitinase; Colorectal cancer; Macrophage; Monocytes.

MeSH terms

  • Carrier Proteins / genetics
  • Chitinases* / metabolism
  • Colorectal Neoplasms* / pathology
  • Humans
  • Macrophages / pathology
  • Prognosis
  • Proto-Oncogene Proteins B-raf / metabolism
  • Survival Rate

Substances

  • Chitinases
  • Proto-Oncogene Proteins B-raf
  • CHID1 protein, human
  • Carrier Proteins