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

• Published in: Cancer chemotherapy and pharmacology Vol. 85; no. 5; pp. 969 - 978
• Main Authors: Su, Jinsong, Dai, Baiyun, Yuan, Weitang, Wang, Guixian, Zhang, Zhiyong, Li, Zhen, Liu, Jinbo, Song, Junmin
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2020; Springer Nature B.V
• Subjects: Blood; Cancer; Cancer Research; Chemotherapy; Colorectal cancer; Colorectal carcinoma; Gene expression; Gene frequency; Gene polymorphism; Genetic diversity; Genotype & phenotype; Genotypes; Genotyping; L1 gene; Medical prognosis; Medicine; Medicine & Public Health; Oncology; Original Article; Patients; PD-L1 protein; Peripheral blood mononuclear cells; Pharmacology/Toxicology; Polymorphism; Prognosis; Regression analysis; Survival; Prognosis; Programmed death-ligand 1; Colorectal cancer; Polymorphism
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-020-04069-1

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.