Oncotarget

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

Zhu Li, Na Li, Fang Li, Zhihua Zhou, Jiao Sang, Zhao Jin, Huihui Liu, Qunying Han, Yi Lv and Zhengwen Liu _

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Oncotarget. 2016; 7:26168-26180. https://doi.org/10.18632/oncotarget.8435

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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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