Folate receptor-α (FOLR1) expression and function in triple negative tumors

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• Folate receptor alpha (FOLR1) is a potential prognostic and therapeutic target in cancer.
• FOLR1 overexpression in breast tumors correlates with poor prognosis.
• Limited data exists on FOLR1 distribution across distinct breast cancer subtypes.

Purpose of the Study:

• To analyze FOLR1 mRNA distribution across estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-positive (HER2+), and triple-negative breast cancer (TNBC) subtypes.
• To investigate the functional role of FOLR1 in TNBC cell lines.
• To identify patient populations that may benefit from targeted anti-FOLR1 therapy.

Main Methods:

• RNA sequencing (RNA-seq) analysis of patient cohorts.
• Immunohistochemical analysis of tissue microarrays.
• RNA interference (RNAi) to deplete FOLR1 in TNBC cell lines.

Main Results:

• FOLR1 mRNA expression was significantly higher in triple-negative/basal tumors compared to ER+ and HER2+ tumors.
• High FOLR1 expression was observed in subsets across all clinical subtypes.
• Immunohistochemistry confirmed higher FOLR1 positivity in triple-negative tumors.
• FOLR1 depletion inhibited growth in TNBC cell lines; overexpression enhanced growth in low folate conditions.
• FOLR1 expression did not correlate with tumor stage or nodal status.

Conclusions:

• Triple-negative breast cancers exhibit significantly higher FOLR1 mRNA expression.
• High FOLR1 expression in TNBC suggests a potential therapeutic target.
• Targeted anti-FOLR1 therapy may benefit patients with triple-negative cancers expressing high FOLR1, offering new treatment options.