Research Papers:
Genetic polymorphisms of immune checkpoint proteins PD-1 and TIM-3 are associated with survival of patients with hepatitis B virus-related hepatocellular carcinoma
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Abstract
Zhu Li1, Na Li1, Fang Li1, Zhihua Zhou1, Jiao Sang1, Zhao Jin1,2, Huihui Liu1,2, Qunying Han1, Yi Lv3,4, Zhengwen Liu1,4
1Department of Infectious Diseases, First Affiliated Hospital of Xi’an Jiaotong University, Xi’ an, 710061, Shaanxi, China
2Xi’an Medical University, Xi’an, 710021, Shaanxi, China
3Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, Shaanxi, China
4Institute of Advanced Surgical Technology and Engineering, Xi’an Jiaotong University, Xi’ an, 710061, Shaanxi, China
Correspondence to:
Zhengwen Liu, email: [email protected]
Keywords: hepatitis B virus, hepatocellular carcinoma, immune checkpoint, PD1, TIM3
Received: February 03, 2016 Accepted: March 14, 2016 Published: March 28, 2016
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.
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