Expression and Clinical Significance of MAPK8, MAPK9, MAP2K4, and MAP2K7 Genes in Colorectal Cancer

Int J Mol Sci. 2025 Dec 22;27(1):100. doi: 10.3390/ijms27010100.

Abstract

This study investigated whether alterations in the expression of genes integral to the c-Jun N-terminal kinase (JNK) signaling pathway play a role in the pathogenesis of colorectal cancer (CRC). It analyzed the expression of genes encoding two JNK isoforms (MAPK8 and MAPK9) and the JNK-activating kinases (MAP2K4 and MAP2K7). Gene expression patterns in CRC tissue were compared with existing data in public online databases to provide an integrated understanding of their potential role in tumorigenesis. The material consisted of 55 cancer tissue fragments collected intraoperatively from patients with histopathologically confirmed CRC. Total RNA isolated from these tissues was used to determine the relative expression of the selected genes using quantitative PCR. Additionally, data from publicly accessible bioinformatics databases were utilized. MAP2K7 gene expression was significantly elevated in tumor specimens with higher histological grades. Conversely, MAPK9 gene expression tended to be higher in tumor tissues with lower histological grades. Moreover, elevated MAPK8 gene expression was linked to an increased incidence of regional lymph node metastasis. Furthermore, bioinformatics analysis confirmed that MAP2K7 and MAPK8 appear to promote tumor aggressiveness and metastasis, whereas MAPK9 and MAP2K4 may have a protective or regulatory role in early stages of the disease.

Keywords: JNK signalling pathway; MAP2K4; MAP2K7; MAPK signalling; MAPK8; MAPK9; PCR; colorectal cancer.

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics
  • Clinical Relevance
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / metabolism
  • Colorectal Neoplasms* / pathology
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lymphatic Metastasis
  • MAP Kinase Kinase 4* / genetics
  • MAP Kinase Kinase 4* / metabolism
  • MAP Kinase Kinase 7* / genetics
  • MAP Kinase Kinase 7* / metabolism
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinase 8* / genetics
  • Mitogen-Activated Protein Kinase 8* / metabolism
  • Mitogen-Activated Protein Kinase 9* / genetics
  • Mitogen-Activated Protein Kinase 9* / metabolism

Substances

  • MAP2K4 protein, human
  • Mitogen-Activated Protein Kinase 8
  • MAP Kinase Kinase 7
  • MAP2K7 protein, human
  • Mitogen-Activated Protein Kinase 9
  • MAP Kinase Kinase 4
  • Biomarkers, Tumor