The influence of PD-L1 genetic variation on the prognosis of R0 resection colorectal cancer patients received capecitabine-based adjuvant chemotherapy: a long-term follow-up, real-world retrospective study

Cancer Chemother Pharmacol. 2020 May;85(5):969-978. doi: 10.1007/s00280-020-04069-1. Epub 2020 Apr 20.

Abstract

Purpose: This study investigated the influence of PD-L1 genetic variation on the prognosis of R0 resection colorectal cancer (CRC) patients who received capecitabine-based adjuvant chemotherapy in real world.

Methods: A total of 315 CRC patients underwent R0 surgical resection and received capecitabine-based adjuvant chemotherapy were included. Clinical characteristics were collected from the hospital record system, prognosis was obtained by telephone follow-up. Peripheral blood and peripheral blood mononuclear cell (PBMC) specimen of CRC patients were performed for the genotyping of polymorphism and mRNA expression of PD-L1, respectively. Analysis on the association between genotypes and prognosis was conducted.

Results: The median disease-free survival (DFS) of the 315 CRC patients was 5.1 years, the median overall survival (OS) was 6.0 years. Regarding the PD-L1 gene polymorphism analysis, the prevalence of 901T>C among the CRC patients was as follows: TT genotype 221 cases (70.16%), TC genotype 86 cases (27.30%), CC genotype 8 cases (2.54%), the minor allele frequency was 0.16, the distribution of three genotypes was in accordance with Hardy-Weinberg equilibrium (P = 0.915). Moreover, the prognosis analysis indicated that the median DFS of patients with TT and TC/CC genotype was 5.4 and 4.0 years, respectively (P = 0.008). The median OS of patients with the two genotypes was 6.4 and 5.0 years (P = 0.007). The multivariate Cox regression analysis showed that the TC/CC genotypes were an independent factor for DFS (odds ratio = 1.56, P = 0.018). Furthermore, the mRNA expression results indicated that the mRNA expression of PD-L1 in PBMC of the patients with TC/CC genotype was significantly higher than patients with TT genotype (P < 0.001).

Conclusion: The prognosis of R0 resection CRC patients received capecitabine-based adjuvant chemotherapy in real world may be influenced by PD-L1 901T>C polymorphism through mediation of the mRNA expression of PD-L1.

Keywords: Colorectal cancer; Polymorphism; Prognosis; Programmed death-ligand 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antimetabolites, Antineoplastic / therapeutic use
  • B7-H1 Antigen / genetics*
  • Capecitabine / therapeutic use*
  • Chemotherapy, Adjuvant / methods
  • China / epidemiology
  • Colectomy / methods*
  • Colorectal Neoplasms* / diagnosis
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / surgery
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Pharmacogenomic Variants
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Retrospective Studies

Substances

  • Antimetabolites, Antineoplastic
  • B7-H1 Antigen
  • CD274 protein, human
  • Capecitabine