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Deciphering Folate Receptor alphaGene Expression and mRNA Signatures in Ovarian Cancer: Implications for Precision Therapies

Title: Deciphering Folate Receptor alphaGene Expression and mRNA Signatures in Ovarian Cancer: Implications for Precision Therapies
Authors: Kfoury, Maria; Finetti, Pascal; Mamessier, Emilie; Bertucci, François; Sabatier, Renaud
Contributors: Institut Paoli-Calmettes (IPC); Fédération nationale des Centres de lutte contre le Cancer (FNCLCC); Centre de Recherche en Cancérologie de Marseille (CRCM); Aix Marseille Université (AMU)-Institut Paoli-Calmettes (IPC); Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Source: ISSN: 1661-6596.
Publisher Information: CCSD; MDPI
Publication Year: 2024
Collection: Aix-Marseille Université: HAL
Subject Terms: [SDV.CAN]Life Sciences [q-bio]/Cancer; [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry; Molecular Biology/Genomics [q-bio.GN]; [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics
Description: International audience ; Antibody–drug conjugates targeting folate receptor alpha (FRα) are a promising treatment for platinum-resistant ovarian cancer (OC) with high FRα expression. Challenges persist in accurately assessing FRα expression levels. Our study aimed to better elucidate FRα gene expression and identify mRNA signatures in OC. We pooled OC gene expression data from 16 public datasets, encompassing 1832 OC and 30 normal ovarian tissues. Additional data included DNA copy number and methylation data from TCGA and protein data from 363 cancer cell lines from the Broad Institute Cancer Cell Line Encyclopedia. FOLR1 mRNA expression was significantly correlated with protein expression in pan-cancer cell lines and ovarian cancer cell lines. FOLR1 expression was higher in OC samples than in normal ovarian tissues (OR = 3.88, p = 6.97 × 10−12). Patients with high FOLR1 expression were more likely to be diagnosed with serous histology, FIGO stage III–IV, and high-grade tumors; however, nearly similar percentages of patients with low FOLR1 expression were also diagnosed with these features. FOLR1 mRNA expression was not correlated with platinum sensitivity or complete surgery, nor with prognosis. However, we identified a 187-gene signature associated with high FOLR1 expression that was significantly associated with improved survival (HR = 0.71, p = 1.18 × 10−6), independently from clinicopathological features. We identified a gene expression signature correlated to high FRα expression and OC prognosis, which may be used to refine therapeutic strategies targeting FRα in OC. These findings warrant validation in larger cohorts.
Document Type: article in journal/newspaper
Language: English
DOI: 10.3390/ijms252211953
Availability: https://hal.science/hal-04945209; https://hal.science/hal-04945209v1/document; https://hal.science/hal-04945209v1/file/ijms-25-11953.pdf; https://doi.org/10.3390/ijms252211953
Rights: https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess
Accession Number: edsbas.D59EEA55
Database: BASE