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

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. <i>FOLR1</i> mRNA expression was significantly correlated with protein expression in pan-cancer cell lines and ovarian cancer cell lines. <i>FOLR1</i> expression was higher in OC samples than in normal ovarian tissues (OR = 3.88, <i>p</i> = 6.97 × 10^-12). Patients with high <i>FOLR1</i> 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 <i>FOLR1</i> expression were also diagnosed with these features. <i>FOLR1</i> mRNA expression was not correlated with platinum sensitivity or complete surgery, nor with prognosis. However, we identified a 187-gene signature associated with high <i>FOLR1</i> expression that was significantly associated with improved survival (HR = 0.71, <i>p</i> = 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.