P4HA2 involved in SLUG-associated EMT predicts poor prognosis of patients with KRAS-positive colorectal cancer

Med Mol Morphol. 2024 Sep;57(3):167-176. doi: 10.1007/s00795-024-00385-0. Epub 2024 Mar 24.

Abstract

This study aimed to examine the immunohistochemical expression of epithelial-mesenchymal transition biomarkers: P4HA2 and SLUG in colorectal carcinoma (CRC) specimens, then to assess their relation to clinicopathological features including KRAS mutations and patients' survival, and finally to study the correlation between them in CRC. The result of this study showed that SLUG and P4HA2 were significantly higher in association with adverse prognostic factors: presence of lympho-vascular invasion, perineural invasion, higher tumor budding, tumor stage, presence of lymph node metastasis, and presence of distant metastasis. CRC specimens with KRAS mutation were associated with significant higher SLUG and P4HA2 expression. High expression of both SLUG and P4HA2 was significantly unfavorable prognostic indicator as regards overall survival (OS) and disease-free survival (DFS). In KRAS mutated cases, high P4HA2 expression was the only significant poor prognostic indicator as regarding DFS. In conclusions, our data highlight that both SLUG and P4HA2 expression may serve as potentially important poor prognostic biomarkers in CRC and targeting these molecules may be providing a novel therapeutic strategy. In KRAS mutation group, high P4HA2 expression is the only independent prognostic factor for tumor recurrence, so it can be suggested to be a novel target for therapy.

Keywords: CRC; P4HA2; SLUG.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor* / genetics
  • Biomarkers, Tumor* / metabolism
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / metabolism
  • Colorectal Neoplasms* / mortality
  • Colorectal Neoplasms* / pathology
  • Disease-Free Survival
  • Epithelial-Mesenchymal Transition* / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Prognosis
  • Prolyl Hydroxylases / genetics
  • Prolyl Hydroxylases / metabolism
  • Proto-Oncogene Proteins p21(ras)* / genetics
  • Snail Family Transcription Factors* / genetics
  • Snail Family Transcription Factors* / metabolism

Substances

  • Biomarkers, Tumor
  • KRAS protein, human
  • Proto-Oncogene Proteins p21(ras)
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • SNAI2 protein, human
  • P4HA2 protein, human
  • Prolyl Hydroxylases