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Deciphering Folate Receptor alphaGene Expression and mRNA Signatures in Ovarian Cancer: Implications for Precision
Maria Kfoury1, Pascal Finetti2, Emilie Mamessier2
1Medical Oncology Department, Institut Paoli-Calmettes, 13009 Marseille, France.
Abstract:
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.
Insights
Targeting folate receptor alpha (FRα) shows promise for ovarian cancer (OC). This study identified a gene signature linked to high FRα expression and improved survival in OC patients, aiding therapeutic strategies.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Antibody-drug conjugates targeting folate receptor alpha (FRα) offer potential for platinum-resistant ovarian cancer (OC).
- Accurate assessment of FRα expression remains a challenge for effective treatment selection.
- Understanding FRα gene expression and associated mRNA signatures in OC is crucial.
Purpose of the Study:
- To investigate FRα gene expression patterns in ovarian cancer.
- To identify mRNA signatures correlated with FRα expression and clinical outcomes in OC.
- To evaluate the potential of FRα-related signatures for refining therapeutic strategies in OC.
Main Methods:
- Pooled gene expression data from 16 public datasets (1832 OC, 30 normal tissues).
- Integrated DNA copy number, methylation (TCGA), and protein expression data (Cancer Cell Line Encyclopedia).
- Analyzed correlations between FOLR1 mRNA, protein expression, clinicopathological features, and survival.
Main Results:
- FOLR1 mRNA expression significantly higher in OC than normal tissues (OR = 3.88, p = 6.97 × 10-12) and correlated with protein levels.
- High FOLR1 expression associated with serous histology, advanced stage, and high grade, but not platinum sensitivity or prognosis.
- A 187-gene signature linked to high FOLR1 expression significantly improved survival (HR = 0.71, p = 1.18 × 10-6), independent of clinical factors.
Conclusions:
- A novel 187-gene expression signature correlates with high FRα expression and improved prognosis in ovarian cancer.
- This signature may help refine therapeutic strategies targeting FRα in OC.
- Further validation in larger cohorts is warranted to confirm these findings.
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