Prognostic Value of TWIST1 and EZH2 Expression in Colon Cancer

J Gastrointest Cancer. 2021 Mar;52(1):90-98. doi: 10.1007/s12029-019-00344-4.

Abstract

Background: Colorectal carcinoma (CRC) is the third most common human cancer. Twist, a basic helix-loop-helix (bHLH) transcription factor, is an epithelial-mesenchymal transition ((EMT) inducer that has been involved in carcinogenesis and chemoresistance. Also, the enhancer of Zeste homolologue2 (EZH2), a member of the polycomb group of genes, had been associated with poor prognosis in several malignancies.

Objective: To evaluate the expression of Twist1 and EZH2 in colon carcinoma in Egyptian patients and its relation to clinicopathological parameters, prognosis, and survival.

Methods: Twist1 and EZH2 expressions were evaluated immunohistochemically in 50 cases of colorectal tumors (12 colon adenomas and 38 colon carcinomas) and 20 samples from normal colonic mucosa.

Results: The expression of Twist1 and EZH2 was significantly higher in colon adenoma and carcinoma than that in normal colonic mucosa (P < 0.05). Twist1 and EZH2 expressions were associated with decreased tumor differentiation, advanced stage, and lymph node metastasis. Twist1 and EZH2 expressions were significantly related to 3-year disease-free survival (P = 0.005 and 0.002 respectively) and 3-year overall survival (P = 0.045 and 0.039, respectively).

Conclusions: Twist1 and EZH2 may serve as prognostic predictors for colon carcinoma and may have a potential role as therapeutic targets in patients with colon carcinoma in the future.

Keywords: Colorectal cancer; EZH2; Immunohistochemistry; Twist1.

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism*
  • Carcinoma / diagnosis
  • Carcinoma / drug therapy
  • Carcinoma / genetics
  • Carcinoma / mortality*
  • Colonic Neoplasms / diagnosis
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / mortality*
  • Disease-Free Survival
  • Egypt / epidemiology
  • Enhancer of Zeste Homolog 2 Protein / analysis
  • Enhancer of Zeste Homolog 2 Protein / metabolism*
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Fluorouracil / therapeutic use
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Leucovorin / therapeutic use
  • Lymphatic Metastasis / genetics
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Nuclear Proteins / analysis
  • Nuclear Proteins / metabolism*
  • Organoplatinum Compounds / therapeutic use
  • Prognosis
  • Prospective Studies
  • Risk Assessment / methods
  • Twist-Related Protein 1 / analysis
  • Twist-Related Protein 1 / metabolism*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Nuclear Proteins
  • Organoplatinum Compounds
  • TWIST1 protein, human
  • Twist-Related Protein 1
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol