Diagnostic and Prognostic Role of TFF3, Romo-1, NF-кB and SFRP4 As Biomarkers for Endometrial and Ovarian Cancers: a Prospective Observational Translational Study

Overview

Journal Arch Gynecol Obstet

Specialty Gynecology & Obstetrics

Date 2022 Apr 24

PMID 35461390

Authors

Hasan Turan

Salvatore Giovanni Vitale

Ilker Kahramanoglu

Luigi Della Corte

Pierluigi Giampaolino

Asli Azemi

Sinem Durmus

Veysel Sal

Nedim Tokgozoglu

Tugan Bese

Macit Arvas

Fuat Demirkiran

Remise Gelisgen

Sennur Ilvan

Hafize Uzun

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Molecular landscape of borderline ovarian tumours: A systematic review.

Sadlecki P, Walentowicz-Sadlecka M Open Med (Wars). 2024; 19(1):20240976.

PMID: 38859878 PMC: 11163159. DOI: 10.1515/med-2024-0976.

Transcriptional expression, prognostic value and immune infiltration of SFRP family in colorectal cancer: a study based on comprehensive bioinformatics and analyses.

Zhou H, Hou H, Hou S, Zhou T Transl Cancer Res. 2023; 12(8):1912-1928.

PMID: 37701102 PMC: 10493803. DOI: 10.21037/tcr-23-152.

Fertility-Sparing Approach in Patients with Endometrioid Endometrial Cancer Grade 2 Stage IA (FIGO): A Qualitative Systematic Review.

Giampaolino P, Cafasso V, Boccia D, Ascione M, Mercorio A, Viciglione F Biomed Res Int. 2022; 2022:4070368.

PMID: 36203482 PMC: 9532104. DOI: 10.1155/2022/4070368.

References

Thim L, May F . Structure of mammalian trefoil factors and functional insights. Cell Mol Life Sci. 2005; 62(24):2956-73. PMC: 11139098. DOI: 10.1007/s00018-005-5484-6. View

Hristova V, Chan D . Cancer biomarker discovery and translation: proteomics and beyond. Expert Rev Proteomics. 2018; 16(2):93-103. PMC: 6635916. DOI: 10.1080/14789450.2019.1559062. View

Giampaolino P, Foreste V, Della Corte L, Di Filippo C, Iorio G, Bifulco G . Role of biomarkers for early detection of ovarian cancer recurrence. Gland Surg. 2020; 9(4):1102-1111. PMC: 7475347. DOI: 10.21037/gs-20-544. View

Amini M, Talebi S, Karimi J . Reactive Oxygen Species Modulator 1 (ROMO1), a New Potential Target for Cancer Diagnosis and Treatment. Chonnam Med J. 2019; 55(3):136-143. PMC: 6769249. DOI: 10.4068/cmj.2019.55.3.136. View

Jacob F, Ukegjini K, Nixdorf S, Ford C, Olivier J, Caduff R . Loss of secreted frizzled-related protein 4 correlates with an aggressive phenotype and predicts poor outcome in ovarian cancer patients. PLoS One. 2012; 7(2):e31885. PMC: 3283709. DOI: 10.1371/journal.pone.0031885. View

Grandi G, Fiocchi F, Cortesi L, Toss A, Boselli F, Sammarini M . The challenging screen detection of ovarian cancer in BRCA mutation carriers adhering to a 6-month follow-up program: results from a 6-years surveillance. Menopause. 2021; 29(1):63-72. DOI: 10.1097/GME.0000000000001883. View

Torre L, Trabert B, DeSantis C, Miller K, Samimi G, Runowicz C . Ovarian cancer statistics, 2018. CA Cancer J Clin. 2018; 68(4):284-296. PMC: 6621554. DOI: 10.3322/caac.21456. View

Vitale S, Riemma G, Ciebiera M, Cianci S . Hysteroscopic treatment of submucosal fibroids in perimenopausal women: when, why, and how?. Climacteric. 2020; 23(4):355-359. DOI: 10.1080/13697137.2020.1754390. View

Pandey V, Zhang M, Chong Q, You M, Raquib A, Pandey A . Hypomethylation associated enhanced transcription of trefoil factor-3 mediates tamoxifen-stimulated oncogenicity of ER+ endometrial carcinoma cells. Oncotarget. 2017; 8(44):77268-77291. PMC: 5652779. DOI: 10.18632/oncotarget.20461. View

10.

Dolcet X, Llobet D, Pallares J, Matias-Guiu X . NF-kB in development and progression of human cancer. Virchows Arch. 2005; 446(5):475-82. DOI: 10.1007/s00428-005-1264-9. View

11.

Gurel C, Inetas G, Hortu I, Tunc E, Kuscu G, Cagirir Dindaroglu F . Cancer and Cancer Stem Cells: New Molecular Perspectives. Crit Rev Oncog. 2019; 24(1):99-104. DOI: 10.1615/CritRevOncog.2019029628. View

12.

Vitale S . The Biopsy Snake Grasper Sec. VITALE: A New Tool for Office Hysteroscopy. J Minim Invasive Gynecol. 2019; 27(6):1414-1416. DOI: 10.1016/j.jmig.2019.12.014. View

13.

Vitale S, Haimovich S, Riemma G, Ludwin A, Zizolfi B, De Angelis M . Innovations in hysteroscopic surgery: expanding the meaning of "in-office". Minim Invasive Ther Allied Technol. 2020; 30(3):125-132. DOI: 10.1080/13645706.2020.1715437. View

14.

Vitale S, Lagana A, Caruso S, Garzon S, Vecchio G, La Rosa V . Comparison of three biopsy forceps for hysteroscopic endometrial biopsy in postmenopausal patients (HYGREB-1): A multicenter, single-blind randomized clinical trial. Int J Gynaecol Obstet. 2021; 155(3):425-432. DOI: 10.1002/ijgo.13669. View

15.

Pohl S, Scott R, Arfuso F, Perumal V, Dharmarajan A . Secreted frizzled-related protein 4 and its implications in cancer and apoptosis. Tumour Biol. 2014; 36(1):143-52. DOI: 10.1007/s13277-014-2956-z. View

16.

El-Balat A, Schmeil I, Karn T, Becker S, Sanger N, Holtrich U . TFF3 Expression as Stratification Marker in Borderline Epithelial Tumors of the Ovary. Pathol Oncol Res. 2017; 24(2):277-282. DOI: 10.1007/s12253-017-0240-4. View

17.

Terris B, Blaveri E, Crnogorac-Jurcevic T, Jones M, Missiaglia E, Ruszniewski P . Characterization of gene expression profiles in intraductal papillary-mucinous tumors of the pancreas. Am J Pathol. 2002; 160(5):1745-54. PMC: 1850868. DOI: 10.1016/S0002-9440(10)61121-2. View

18.

Della Corte L, Giampaolino P, Mercorio A, Riemma G, Schiattarella A, De Franciscis P . Sentinel lymph node biopsy in endometrial cancer: state of the art. Transl Cancer Res. 2022; 9(12):7725-7733. PMC: 8797296. DOI: 10.21037/tcr.2020.04.21. View

19.

May F, Westley B . TFF3 is a valuable predictive biomarker of endocrine response in metastatic breast cancer. Endocr Relat Cancer. 2015; 22(3):465-79. PMC: 4455223. DOI: 10.1530/ERC-15-0129. View

20.

Xiao P, Ling H, Lan G, Liu J, Hu H, Yang R . Trefoil factors: Gastrointestinal-specific proteins associated with gastric cancer. Clin Chim Acta. 2015; 450:127-34. DOI: 10.1016/j.cca.2015.08.004. View