Prognostic and clinicopathological significance of TMEFF2, SMOC-2, and SOX17 expression in endometrial carcinoma

Exp Mol Pathol. 2021 Oct:122:104670. doi: 10.1016/j.yexmp.2021.104670. Epub 2021 Jul 31.

Abstract

Background there is a need for novel biomarkers and targeting therapies for predicting Endometrial carcinoma (EC) progression and recurrence. TMEFF2 is a gene that was found to play a role in EMT. SMOC-2 is expressed in embryogenesis and it was identified as a recent stem cell-related gene that has a role in cancer progression. SRY-box 17 (SOX17) is a member of the SRY-related HMG-box (SOX) family of transcription factors. Dysregulation or downregulation of SOX17 expression was found in many cancer tissues.

Aim: In the present study, we aimed to assess the tissue protein expressions of TMEFF2, SMOC-2, and SOX17 in EC using immunohistochemistry to evaluate their clinicopathological values and prognostic roles in EC patients.

Patients and methods: This is prospective cohort study included 120 patients with EC. Sections from 120 paraffin blocks were retrieved and stained with TMEFF2, SMOC-2, and SOX17 using immunohistochemistry, the expression of markers in all tissue samples was assessed, analyzed and correlation of pathological parameters with the levels of expression was done. All patients were followed up till death or till the last known alive data for about 50 months (range from 25 to 60).

Results: TMEFF2, SMOC-2 expression was correlated with the presence of lymph node metastases (p = 0.023), distant metastasis (p = 0.039) recurrence of the tumor after successful therapy, overall survival, and disease-free survival (p < 0.001). SOX17 positive expression was positively correlated with low grade (p = 0.019), absence of lymph node metastasis (p = 0.001), absence of distant metastasis (p = 0.013), low stage (p = 0.03), and its negative expression was positively correlated with recurrence of the tumor after successful therapy, overall survival and disease-free survival (p = 0.001). In conclusion, we demonstrated that both TMEFF2 and SMOC-2 were highly expressed in EC and were associated with a shortened survival rate, dismal outcome, and poor prognosis in EC patients. While SOX17 expression was related to a favorable outcome and its down-regulation was associated with dismal EC patient's survival.

Keywords: Endometrial carcinoma; Immunohistochemistry; Prognosis; SMOC-2; SOX17; TMEFF2.

MeSH terms

  • Adult
  • Biomarkers, Tumor / genetics
  • Calcium-Binding Proteins / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease-Free Survival
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / pathology
  • Membrane Proteins / genetics*
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Prognosis
  • SOXF Transcription Factors / genetics*

Substances

  • Biomarkers, Tumor
  • Calcium-Binding Proteins
  • Membrane Proteins
  • Neoplasm Proteins
  • SMOC2 protein, human
  • SOX17 protein, human
  • SOXF Transcription Factors
  • TMEFF2 protein, human