Diagnostic and prognostic role of TFF3, Romo-1, NF-кB and SFRP4 as biomarkers for endometrial and ovarian cancers: a prospective observational translational study

Arch Gynecol Obstet. 2022 Dec;306(6):2105-2114. doi: 10.1007/s00404-022-06563-8. Epub 2022 Apr 24.


Purpose: This study aimed to evaluate trefoil factor 3 (TFF3), secreted frizzled-related protein 4 (sFRP4), reactive oxygen species modulator 1 (Romo1) and nuclear factor kappa B (NF-κB) as diagnostic and prognostic markers of endometrial cancer (EC) and ovarian cancer (OC).

Methods: Thirty-one patients with EC and 30 patients with OC undergone surgical treatment were enrolled together with 30 healthy controls in a prospective study. Commercial ELISA kits determined serum TFF-3, Romo-1, NF-кB and sFRP-4 concentrations.

Results: Serum TFF-3, Romo-1 and NF-кB levels were significantly higher in patients with EC and OC than those without cancer. Regarding EC, none of the serum biomarkers differs significantly between endometrial and non-endometrioid endometrial carcinomas. Mean serum TFF-3 and NF-кB levels were significantly higher in advanced stages. Increased serum levels of TFF-3 and NF-кB were found in those with a higher grade of the disease. Regarding OC, none of the serum biomarkers differed significantly among histological subtypes. Significantly increased serum levels of NF-кB were observed in patients with advanced-stage OC than those with stage I and II diseases. No difference in serum biomarker levels was found between those who had a recurrence and those who had not. The sensibility and specificity of these four biomarkers in discriminating EC and OC from the control group showed encouraging values, although no one reached 70%.

Conclusions: TFF-3, Romo-1, NF-кB and SFRP4 could represent new diagnostic and prognostic markers for OC and EC. Further studies are needed to validate our results.

Keywords: Biomarkers; Endometrial cancer; NF-кB; Ovarian cancer; Romo-1; SFRP4; TFF-3.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Female
  • Humans
  • Membrane Proteins
  • Mitochondrial Proteins
  • NF-kappa B* / metabolism
  • Ovarian Neoplasms* / diagnosis
  • Ovarian Neoplasms* / metabolism
  • Prognosis
  • Prospective Studies
  • Proto-Oncogene Proteins
  • Trefoil Factor-3


  • NF-kappa B
  • Biomarkers
  • TFF3 protein, human
  • Trefoil Factor-3
  • SFRP4 protein, human
  • Proto-Oncogene Proteins
  • ROMO1 protein, human
  • Membrane Proteins
  • Mitochondrial Proteins