Genetic polymorphisms of immune checkpoint proteins PD-1 and TIM-3 are associated with survival of patients with hepatitis B virus-related hepatocellular carcinoma.

Abstract

Programmed cell death protein 1 (PD-1) and T-cell immunoglobulin domain and mucin domain containing molecule 3 (TIM-3) are involved in hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). This study examined the associations of PD1 and TIM3 polymorphisms with the overall survival (OS) of a prospective cohort of 258 HBV-related HCC patients. Results showed that PD1 +8669 G allele-containing genotypes or TIM3 -1516 genotype GG were significantly associated with longer OS (P < 0.001 and P = 0.001, respectively). In multivariate analysis, PD1 +8669 G allele-containing genotypes and TIM3 -1516 genotype GG were independently associated with longer OS (hazard ratio (HR), 1.835; 95% confidence interval (CI), 1.342-2.509; P < 0.001 and HR, 2.070; 95%CI, 1.428-3.002; P < 0.001, respectively). PD1 +8669 G allele-containing genotypes were significantly associated with longer OS in patients receiving surgical (resection or radiofrequency) treatment, transcatheter arterial chemoembolization (TACE) or supportive and symptomatic treatment. TIM3 -1516 genotype GG was significantly associated with longer OS in TACE patients. In multivariate analysis, PD1 +8669 G allele-containing genotypes were independently associated with longer OS in each treatment population. TIM3 -1516 genotype GG was independently associated with longer OS in patients receiving surgical treatment or TACE. These findings suggest that PD1 +8669 A/G and TIM3 -1516 G/T polymorphisms may affect the prognosis of HBV-related HCC and may be new predictors of prognosis for HCC patients.

• Authors: Zhu Li, Na Li, Fang Li, Zhihua Zhou, Jiao Sang, Zhao Jin, Huihui Liu, Qunying Han, Yi Lv, Zhengwen Liu
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 18 Pg. 26168-80 (May 03 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27034168 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• HAVCR2 protein, human
• Hepatitis A Virus Cellular Receptor 2
• PDCD1 protein, human
• Programmed Cell Death 1 Receptor

Topics

• Adult
• Aged
• Biomarkers, Tumor (genetics)
• Carcinoma, Hepatocellular (genetics, mortality, virology)
• Female
• Follow-Up Studies
• Genetic Predisposition to Disease
• Genotype
• Hepatitis A Virus Cellular Receptor 2 (genetics)
• Hepatitis B (genetics, mortality, virology)
• Hepatitis B virus (pathogenicity)
• Humans
• Liver Neoplasms (genetics, mortality, virology)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Prognosis
• Programmed Cell Death 1 Receptor (genetics)
• Prospective Studies
• Survival Rate
• Young Adult