Study on the expression level of folate receptor γ in thyroid cancer and its association with clinicopathological characteristics

Despite generally favorable outcomes, identifying reliable biomarkers remains crucial for managing aggressive subtypes of thyroid cancer. The present study aimed to investigate the association between folate receptor γ (FOLR3) expression and the clinicopathological features of thyroid cancer, and to explore its clinical relevance using bioinformatics and experimental approaches, ultimately assessing its potential value as a diagnostic and therapeutic biomarker. Differential expression analysis of RNA‑sequencing data from The Cancer Genome Atlas database was performed to identify the differentially expressed gene FOLR3, followed by standard single‑cell analysis. Clinicopathological data from 293 patients with thyroid cancer were collected to investigate pathological characteristics and FOLR3 expression, which was further validated using immunohistochemistry. The functional effects of FOLR3 on the malignant behavior of thyroid cancer cells were assessed using colony formation, Cell Counting Kit‑8, scratch wound healing and Transwell invasion assays. FOLR3 expression was significantly higher in normal thyroid tissue compared with cancer tissues (P<0.001). FOLR3 expression level was associated with capsular invasion, perineural invasion, striated muscle invasion and pT stage (all P<0.05). Functional experiments demonstrated that FOLR3 suppressed the proliferation, migration and invasion of TPC‑1 cells (all P<0.05). In conclusion, FOLR3 expression is generally low or absent in thyroid cancer, particularly in cases demonstrating pronounced local infiltration, indicating its potential as a diagnostic biomarker for the evaluation of tumor invasiveness. Patients with high FOLR3 expression exhibit a higher survival rate, suggesting its potential prognostic value. FOLR3 inhibits the progression of thyroid cancer by inhibiting the STAT3/MAPK signaling pathways and reprogramming folate metabolism, highlighting its potential as a therapeutic target for thyroid cancer in the future.