Identifying Genetic Targets in Gynecological Tumors

NCT ID: NCT07169396

Last Updated: 2025-09-11

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 180 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-11-17
• Study Completion Date: 2027-11-30

Brief Summary

This observational study aims to identfy genetic targets involved in the pathogenesis of gynecological tumors, with a focus on high-grade serous ovarian carcinoma. Using a triple approach - in silico, ex vivo and in vitro - the study will investigate the role of gonadotropins and their related signaling pathways in the epithelial ovarian cancers. Gene and protein expression levels will be evaluated through transcriptomic analysis, immunohistochemistry and functional assays on tumor cell lines. The goal is to uncover potential diagnostic or therapeutic targets in gynecological malignancies.

Detailed Description

Ovarian cancer is the leading cause of death among gynecological malignanciens. High-grade serous ovarian carcinoma (HGSOC) represents the most common and aggressive subtype. Growing evidence suggests that gonadotropins and their receptors (FSHR and LHCGR), as well as membrane estrogen receptors (GPER), may play a significant role in ovarian carcinogenesis by modulating proliferative and anti-apoptotic signals. The GEN EX CO 2021 study is a monocentric, observational project conducted at AUSL-IRCCS Reggio Emilia. It is both prospective and retrospective, and it aims to identify gene expression patterns that differentiate ovarian tumor tissues from normal ovarian epithelium. The study uses a triple experimental approach:

• In silico: differentially expressed genes were identified from public datasets (GSE18521 and GSE26712) via transcriptomic analysis and pathway analysis;
• Ex vivo: mRNA and protein expression will be assessed in fresh-frozen and FFPE tissue samples from patients with HGSOC and other rare epithelial ovarian tumor subtypes (e.g., mesonephric-like, mucinous, endometrioid, clear cell);
• In vitro: functional experiments using ovarian cancer cell lines (e.g., A2780, KGN, HGL5) will evaluate the effects of gene overexpression or silencing on cell viability, apoptosis and proliferation.

Participants include both prospective cases and retrospective samples, as well as control tissues from patients undergoing surgery for benign conditions. Gene expressions will be assessed through digital PCR, while protein levels will be analyzed via immunohistochemistry. Functional studies will explore the biological impact of selected genes on tumor cell behavior. Data will be collected using a secure, coded e-CRF in compliance with ethical and privacy regulations. The ultimate goal is to identify novel molecular targets that could inform future diagnostic or therapeutic approaches in ovarian cancer.

Conditions

Ovarian Cancer

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: OTHER

Study Groups

Ovarian Cancer

Participants with high-grade serous ovarian carcinoma (HGSOC) or other rare epithelial ovarian tumor subtypes (e.g., mucinous, endometrioid, clear cell, mesonephric-like). Includes both prospectively enrolled patients and retrospectively collected samples. Purpose: to analyze gene and protein expression profiles in tumor tissues and compare them with normal ovarian epithelium.

RNA extraction and gene expression

Intervention Type: OTHER

RNA extraction and gene expression

Control group

Patients undergoing surgery for benign gynecological conditions, from whom non-tumoral ovarian epithelial tissue is obtained. Purpose: to provide baseline biological controls for comparison with ovarian cancer samples.

RNA extraction and gene expression

Intervention Type: OTHER

RNA extraction and gene expression

Interventions

RNA extraction and gene expression

RNA extraction and gene expression

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Adult women ≥18 years old
• Histologically confirmed diagnosis of epithelial ovarian cancer (including high- grade serous, endometrioid, mucinous, clear cell, or mesonephric-like histotypes)
• Signed informed consent (for prospective cases) or ethically approved waiver (for retrospective samples)

Exclusion Criteria

• Refusal to sign informed consent
• Diagnosis of low-grade or non-epithelial ovarian tumors
• Patients whose clinical or pathological data are unavailable or insufficient for study inclusion

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Azienda USL Reggio Emilia - IRCCS

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Azienda USL IRCCS di Reggio Emilia

Reggio Emilia, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Beatrice Melli, MD

Role: CONTACT

beatrice.melli@ausl.re.it

0522-29577

Facility Contacts

Jasmine Lonetti

Role: primary

jasmine.lonetti@ausl.re.it

References

Zheng W, Lu JJ, Luo F, Zheng Y, Feng Yj, Felix JC, Lauchlan SC, Pike MC. Ovarian epithelial tumor growth promotion by follicle-stimulating hormone and inhibition of the effect by luteinizing hormone. Gynecol Oncol. 2000 Jan;76(1):80-8. doi: 10.1006/gyno.1999.5628.

Reference Type: BACKGROUND

PMID: 10620446 (View on PubMed)

Zhang Z, Jia L, Feng Y, Zheng W. Overexpression of follicle-stimulating hormone receptor facilitates the development of ovarian epithelial cancer. Cancer Lett. 2009 Jun 8;278(1):56-64. doi: 10.1016/j.canlet.2008.12.024. Epub 2009 Jan 31.

Reference Type: BACKGROUND

PMID: 19181441 (View on PubMed)

Czogalla B, Partenheimer A, Jeschke U, von Schonfeldt V, Mayr D, Mahner S, Burges A, Simoni M, Melli B, Benevelli R, Bertini S, Casarini L, Trillsch F. beta-arrestin 2 Is a Prognostic Factor for Survival of Ovarian Cancer Patients Upregulating Cell Proliferation. Front Endocrinol (Lausanne). 2020 Sep 18;11:554733. doi: 10.3389/fendo.2020.554733. eCollection 2020.

Reference Type: BACKGROUND

PMID: 33042017 (View on PubMed)

Casarini L, Lazzaretti C, Paradiso E, Limoncella S, Riccetti L, Sperduti S, Melli B, Marcozzi S, Anzivino C, Sayers NS, Czapinski J, Brigante G, Poti F, La Marca A, De Pascali F, Reiter E, Falbo A, Daolio J, Villani MT, Lispi M, Orlando G, Klinger FG, Fanelli F, Rivero-Muller A, Hanyaloglu AC, Simoni M. Membrane Estrogen Receptor (GPER) and Follicle-Stimulating Hormone Receptor (FSHR) Heteromeric Complexes Promote Human Ovarian Follicle Survival. iScience. 2020 Nov 18;23(12):101812. doi: 10.1016/j.isci.2020.101812. eCollection 2020 Dec 18.

Reference Type: BACKGROUND

PMID: 33299978 (View on PubMed)

Other Identifiers

676/2021/TESS/AUSLRE

Identifier Type: -

Identifier Source: org_study_id