Influence of PD-L1 gene polymorphism on the survival of colorectal cancer patients undergoing capecitabine-based adjuvant chemotherapy / 医学研究生学报

ABSTRACT

Objective Programmed death-ligand 1 (PD-L1) is essential in the immune escape of colorectal cancer (CRC) cells. In this study, we investigated the disease-free survival (DFS) and overall survival (OS) of CRC patients receiving capecitabine-based adjuvant chemotherapy after RO resection. Methods This retrospective study included 265 CRC patients treated by RO resection and postoperative capecitabine-based adjuvant chemotherapy in Zhengzhou People′s Hospital between January 1, 2010 and December 12, 2017. We analyzed the clinical data, performed genotyping of the genetic variants and determined the expression of PD-L1 mRNA in the CRC tissue. We also analyzed the correlation between the genetic polymorphisms and other baseline characteristics by chi-square test, the expression of PD-L1 mRNA in different genotypes by non-parametric test, and the prognosis using the Kaplan-Meier method, followed by multivariate Cox regression analysis for adjustment. Results The median DFS and OS of the 265 CRC patients were 4.6 and 6.5 years, respectively. Three single nucleotide polymorphisms of the PD-L1 gene, 901T>C, -1813G>C and -1457T>A, were identified in the NCBI database with the minor allele frequency >10% in the Chinese population, of which, only 901T>C was of clinical significance in the outcome analysis. 901T>C was located in the intron region of the PD-L1 gene, with the genotypes of TT in 185 cases (69.81%), TC in 72 (27.17%) and CC in 8 (3.02%). The minor allele frequency was 0.17 and the distribution frequencies of all the three genotypes conformed to the Hardy-Weinberg equilibrium (P = 0.758). The median DFS was significantly longer in the CRC patients with the TT genotype than in those with the TC or CC genotype (4.8 vs 3.5 years, P = 0.001), and so was the median OS (6.7 vs 4.7 years, P < 0.001). The adjustment of OS by multivariate Cox regression analysis showed that the TC and CC genotypes were an independent factor for OS (OR = 1.89, P = 0.006). The analysis of 89 of the CRC tissue specimens revealed a markedly higher expression of PD-L1 mRNA in the patients with the TC or CC genotype than in those with the TT genotype (P < 0.001). Conclusion The 901T>C polymorphism of the PD-L1 gene may influence the clinical outcomes of the CRC patients receiving capecitabine-based adjuvant chemotherapy by mediating the expression of PD-L1 mRNA.