Influence of programmed death-ligand 1 genetic variation on the clinical outcomes of postoperative CRC patients received 5-FU based adjuvant chemotherapy

doi:10.12092/j.issn.1009-2501.2019.02.010

Abstract

Abstract:

AIM: To investigate the association between PD-L1 genetic variation and clinical outcomes of postoperative CRC patients received 5-FU based adjuvant chemotherapy. METHODS: Designed as a retrospective analysis, a total of 213 CRC patients who underwent surgical treatment and received 5-FU based adjuvant chemotherapy were included in this study. Baseline characteristics and the clinical outcomes data of the patients included in this study were managed. Peripheral blood and the postoperative tissue specimen of the CRC patients were collected for the genotyping of the genetic variation and PD-L1 mRNA expression, respectively. The correlation between genetic variation and other baseline characteristics was analyzed by chi square test and non-parametric test. The mRNA expression of PD-L1 in different genotypes was analyzed by non-parametric test. The univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, and multivariate was adjusted by Cox regression analysis. RESULTS:The single nucleotide polymorphism included in this this study were collected in the NCBI database with the minor allele frequency >10% in Chinese population (901T>A, -1813G>C and -1349T>A). Of the polymorphisms analyzed, only 901T>A was of clinical significance. Located in the Intron region, the prevalence of 901T>A among the CRC patients were as follows: TT genotype 148 cases (69.48%), TC genotype 59 cases (27.70%), CC genotype 6 cases (2.82%), the minor allele frequency was 0.17.The distribution of three genotypes was in accordance with Hardy-Weinberg Equilibrium (P=0.967). TC genotype and CC genotype patients were merged in the comparison of prognosis. The survival analysis of patients with different genotypes found that the median Disease-free survival (mDFS) of patients with TT and TC/CC genotypes was 4.7 and 3.3 years, which was statistically significant (P=0.001). In terms of overall survival (OS), the median OS (mOS) of the two genotypes were 6.5 and 4.7 years respectively, which was statistically significant as well (P<0.001). Adjusted in multivariate Cox regression analysis for OS, TC/CC genotype was an independent factor for OS (OR=1.89, P=0.006). Additionally, of the 79 postoperative tissue specimens, the results showed that the mRNA expression of PD-L1 in cancer tissues of the patients with TC/CC genotypes were significantly higher than those of the TT genotype patients (P<0.001). CONCLUSION: The clinical outcomes of CRC patients receiving 5-FU based adjuvant chemotherapy may be influenced by PD-L1 901T>A through mediating the mRNA expression of PD-L1.

Key words: colorectal cancer, programmed death-ligand 1, polymorphism, prognosis

CLC Number:

R735.3

BAI Yan, ZHENG Xiaoyong, YANG Yage, FANG Lifeng. Influence of programmed death-ligand 1 genetic variation on the clinical outcomes of postoperative CRC patients received 5-FU based adjuvant chemotherapy[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(2): 180-187.

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