Expression of epithelial-mesenchymal transition biomarkers: Discoidin domain receptor 2, Snail-1, and Ovol-2 as predictors of clinical outcome in patients with epithelial ovarian carcinoma

J Cancer Res Ther. 2022 Jul-Sep;18(4):1073-1082. doi: 10.4103/jcrt.JCRT_605_19.

Abstract

Context: Discoidin domain receptor 2 (DDR-2), which belongs to the receptor tyrosine kinase family, Snail-1, which is a member of zinc-finger transcription factor family, and Ovol-2, which is a member of Ovol family, are incriminated in epithelial-mesenchymal transition (EMT) during cancer progression.

Aim: In the current study, we aim to clarify the extent to which EMT biomarkers, DDR-2, Snail-1, and Ovol-2 expression, are involved in the progression of EOC aiming at identification of novel markers for predicting the prognosis of EOC patients.

Settings and design: This was a prospective cohort that was performed in the Faculty of Medicine, Zagazig University.

Materials and methods: We evaluated DDR-2, Snail-1, and Ovol-2 expression in 60 patients of EOC using immunohistochemistry. We followed our patients for about 36 months and analyzed the relationship between markers expression and the prognosis of patients.

Statistical analysis used: SPSS program (Statistical Package for the Social Sciences).

Results: High expression of both DDR-2 and Snail-1 was related to higher grade (P = 0.006) and advanced FIGO stage of the tumor (P < 0.001). Ovol-2 high expression was associated with lower grade of the tumor (P = 0.002) and early stage of the tumor (P < 0.001). High Ovol-2 and low DDR2 and Snail-1 expression were strongly correlated with better response to therapy (P = 0.003 and 0.005, respectively) and increased 3-year survival rates (P < 0.001).

Conclusion: DDR-2 and Snail-1 are markers of poor prognosis in EOC while Ovol-2 is a marker of good prognosis.

Keywords: Discoidin domain receptor 2; Ovol-2; Snail-1; epithelial ovarian carcinoma; epithelial–mesenchymal transition; immunohistochemistry; prognosis.

MeSH terms

  • Biomarkers
  • Biomarkers, Tumor
  • Carcinoma, Ovarian Epithelial
  • Discoidin Domain Receptor 2*
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Humans
  • Ovarian Neoplasms* / pathology
  • Prognosis
  • Prospective Studies
  • Snail Family Transcription Factors / genetics
  • Snail Family Transcription Factors / metabolism
  • Transcription Factors / metabolism
  • Zinc

Substances

  • Biomarkers
  • Biomarkers, Tumor
  • Snail Family Transcription Factors
  • Transcription Factors
  • Discoidin Domain Receptor 2
  • Zinc