Expression of the Folate Receptor Proteins FOLR1 and FOLR2 in Correlation With Clinicopathological Variables of Gastric Cancer.

ABSTRACT

INTRODUCTION: Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, owing to its aggressive nature and poor prognosis. The role of folate receptors, particularly folate receptor 1 (FOLR1) and folate receptor 2 (FOLR2), in cancer has been increasingly recognized due to their overexpression in various malignancies including gastric cancer, and its potential implications in cancer progression, treatment resistance and as therapeutic targets. OBJECTIVE: To evaluate the expression patterns of FOLR1 and FOLR2 in GC patients' tissue and blood specimens and to correlate these patterns with clinicopathological variables. METHODS: A total of 58 gastric cancer patients were enrolled at the Regional Cancer Centre (RCC) from March 2017 to March 2020. Immunohistochemical analysis was performed to examine the expression of FOLR1 and FOLR2 in formalin-fixed paraffin-embedded (FFPE) tissue samples. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to analyze FOLR1 and FOLR2 expression in blood samples. Statistical analyses were conducted using chi-square tests, independent T-tests, and Kaplan-Meier survival analysis. RESULTS: FOLR1 and FOLR2 were overexpressed in 82.76% and 70.69% of gastric cancer tissues, respectively. High expression levels of FOLR1 were significantly associated with the diffuse type of gastric cancer (p<0.005). qRT-PCR showed significant overexpression of FOLR1 in gastric cancer blood samples compared to control samples, with a median fold change of approximately 14.18 times. Conversely, FOLR2 was significantly underexpressed in gastric cancer samples, with a fold change of 0.30. However, no significant correlation was found between FOLR2 expression and the clinicopathological features. The overall survival analysis did not show a significant difference in survival rates based on the expression levels of FOLR1 and FOLR2. CONCLUSIONS: This study highlights the differential expression patterns of FOLR1 and FOLR2 in gastric cancer and underscores the complexity of their roles in cancer biology. While FOLR1 shows potential as a biomarker for gastric cancer due to its overexpression, further studies are needed to fully elucidate the therapeutic and prognostic implications of folate receptors in gastric cancer.