title: 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.affiliation: Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi' an, 710061, Shaanxi, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi' an, 710061, Shaanxi, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi' an, 710061, Shaanxi, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi' an, 710061, Shaanxi, China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi' an, 710061, Shaanxi, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Sang
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi' an, 710061, Shaanxi, China.|Xi'an Medical University, Xi'an, 710021, Shaanxi, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi' an, 710061, Shaanxi, China.|Xi'an Medical University, Xi'an, 710021, Shaanxi, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi' an, 710061, Shaanxi, China.
authors.forename: Qunying
authors.initials: Q
authors.lastname: Han
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.|Institute of Advanced Surgical Technology and Engineering, Xi'an Jiaotong University, Xi' an, 710061, Shaanxi, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi' an, 710061, Shaanxi, China.|Institute of Advanced Surgical Technology and Engineering, Xi'an Jiaotong University, Xi' an, 710061, Shaanxi, China.
authors.forename: Zhengwen
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000401:mortality* / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D000072597:Hepatitis A Virus Cellular Receptor 2 / Q000235:genetics*; D006509:Hepatitis B / Q000235:genetics / Q000401:mortality* / Q000821:virology; D006515:Hepatitis B virus / Q000472:pathogenicity; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000401:mortality* / Q000821:virology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics*; D011446:Prospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: PD1; TIM3; hepatitis B virus; hepatocellular carcinoma; immune checkpoint