FOLR1 was up-regulated in cervical squamous cell carcinoma and correlated with the patients’ progression free survival

Abstract

Abstract Objective The aim of the present work was to evaluate the folate-receptor 1 (FOLR1) expression in cervical squamous cell carcinoma and its clinical significance. Methods FOLR1 mRNA expression level was detected in the cancer genome atlas (TCGA) database for multiple carcinomas. The FOLR1 mRNA relative expression between tumor tissue and normal cervix tissue of the cervical squamous cell cancer patients was compared by the online data analysis tool of GEPIA. The overall survival (OS) and progression free survival (PFS) between the FOLR1 high and low expression groups were compared by the log-rank test. Thirty one cervical squamous cancer patients and 20 healthy controls were included in and tested for serum FOLR1 protein level detection. Eighty one cervical squamous cell cancer patients who received surgery were included for FOLR1 protein expression detected by immunohistochemistry assay (IHC). The correlation between FOLR1 protein expression and patients’ clinical features was analyzed. Results FOLR1 mRNA was up-regulated in tumor tissue compared to corresponding normal cervical tissue of cervical squamous cell carcinoma. Top 20 genes interacted with FOLR1 was identified through the network with the edges of 146. UBXN10 (r=0.668, P<0.01) and GBP6 (r-=0.606, P<0.01) were the top 2 genes that most correlated with FOLR1. The serum level of FR-α (FOLR1 coding protein) were 275.50±83.79 and 161.70±66.62 (ng/L) for the cervical cancer and healthy control subjects respectively with significant statistical difference (P<0.05). Using the serum FR-α as serological marker for cervical cancer detection, the diagnostic sensitivity, specificity and AUC were 80.0% (58.40% to 91.93%), 80.65% (63.72% to 90.81%) and 0.85(95%CI:0.74-0.96), respectively. Immunohistochemical assay indicated that of the 81 cancer tissue samples, 45 (55.6%) was FOLR1 protein positive. FOLR1 protein positive expression rate in FIGO stage Ⅲ/Ⅳ was significant higher than in the stage Ⅰ/Ⅱ with statistical difference (P<0.05). The progression free survival (PFS) was significant different between FOLR1 high and low expression group (HR=2.48, 95%CI:1.1-5.58, P=0.023). However, the overall survival (OS) was not statistical different between the two groups (HR=1.34, 95%CI:0.84-2.15, P=0.22). Conclusion: FOLR1 was up-regulated in both serum and cancer tissue of cervical squamous cell carcinoma which may act as diagnostic and prognostic maker for cervical squamous cell cancer.