Abstract
PURPOSE: This study aims to evaluate the feasibility of using immune checkpoint-related gene polymorphisms and serum levels of PD-1, PD-L1 and CTLA4 in predicting chemotherapy resistance in patients with cervical cancer. METHODS: Seven candidate SNPs in PDCD1, CD274 and CTLA4 were genotyped in 1032 cervical cancer patients (537 non-responders and 495 responders based on their responses to chemotherapy), and the serum level of PD-1, PD-L1 and CTLA4 was detected by ELISA. RESULTS: The frequencies of minor allele A of PDCD1- rs2227982, CD274-rs2890658 and CTLA4-rs3087243 were significantly higher in non-responders than that in responders (p ≤ 0.0001). Moreover, the genotype AA of the three SNPs was associated with a 2.24, 3.78 and 2.71-fold increase in susceptibility to platinum resistance, respectively (p ≤ 0.0001). In addition, all of the three SNPs were associated with the risk of cisplatin resistance in both patients with squamous cell carcinoma and adenocarcinoma under different genetic models (p <0.05). The serum concentrations of PD-L1 and CTLA4 in the non-responder group were significantly higher than those in the responder group (p < 0.0001). Moreover, the PD-L1 and CTLA4 levels of carriers with mutant genotypes of CD274-rs2890658 and CTLA4-rs3087243 were significantly higher than those of with wild-type, and the serum levels of homozygous mutant carriers were even higher (p < 0.0001). CONCLUSION: The PDCD1- rs2227982, CD274-rs2890658 and CTLA4- rs3087243 polymorphisms and high serum levels of PD-L1 and CTLA4 may predict chemotherapy resistance in cervical cancer patients.