Histaminergic System and Inflammation-Related Genes in Normal Large Intestine and Adenocarcinoma Tissues: Transcriptional Profiles and Relations

Int J Mol Sci. 2023 Mar 3;24(5):4913. doi: 10.3390/ijms24054913.

Abstract

Transcriptional analyses such as microarray data have contributed to the progress in the diagnostics and therapy of colorectal cancer (CRC). The need for such research is still present because of the disease being common in both men and women with a high second position in cancer rankings. Little is known about the relations between the histaminergic system and inflammation in the large intestine and CRC. Therefore, the aim of this study was to evaluate the expression of genes related to the histaminergic system and inflammation in the CRC tissues at three cancer development designs: all tested CRC samples, low (LCS) and high (HCS) clinical stage, and four clinical stages (CSI-CSIV), to the control. The research was carried out at the transcriptomic level, analysing hundreds of mRNAs from microarrays, as well as carrying out RT-PCR analysis of histaminergic receptors. The following histaminergic mRNAs: GNA15, MAOA, WASF2A, and inflammation-related: AEBP1, CXCL1, CXCL2, CXCL3, CXCL8, SPHK1, TNFAIP6, were distinguished. Among all analysed transcripts, AEBP1 can be considered the most promising diagnostic marker in the early stage of CRC. The results showed 59 correlations between differentiating genes of the histaminergic system and inflammation in the control, control and CRC, and CRC. The tests confirmed the presence of all histamine receptor transcripts in both the control and colorectal adenocarcinoma. Significant differences in expression were stated for HRH2 and HRH3 in the advanced stages of CRC adenocarcinoma. The relations between the histaminergic system and inflammation-linked genes in both the control and the CRC have been observed.

Keywords: adenocarcinoma; colorectal cancer; histaminergic system; inflammation; intestine; microarray; transcriptional analysis.

MeSH terms

  • Adenocarcinoma* / pathology
  • Carboxypeptidases
  • Colorectal Neoplasms* / pathology
  • Female
  • Gene Expression Profiling
  • Humans
  • Inflammation
  • Intestine, Large / metabolism
  • Male
  • Repressor Proteins / genetics

Substances

  • AEBP1 protein, human
  • Carboxypeptidases
  • Repressor Proteins

Grants and funding

This research was funded by the Medical University of Silesia grant number PCN-1-064/N/1/F.