目的：探讨人内源性逆转录病毒-H 长末端重复关联蛋白 2（human endogenous retrovirus subfamily H long terminal repeat associating protein 2，HHLA2）在肝细胞癌（hepatocellular carcinoma，HCC）组织中的表达及其与HCC患者临床病理特征和预后的关系。方法：基于TCGA数据库分析人HCC组织中HHLA2 mRNA表达与B7家族基因的相关性，用组织芯片技术、免疫组织化学染色法分别检测90例HCC组织及其癌旁组织中HHLA2的表达。用Wilcoxon秩和检验比较HCC组织及癌旁组织中HHLA2 表达水平的差异，用 χ2检验分析 HCC 组织中 HHLA2 表达水平与患者临床病理特征的关系，用 Kaplan-Meier 法分析HHLA2表达水平与患者总生存期（OS）的关系，拟合Cox模型评价不同指标的预后价值。结果：HCC组织中HHLA2 mRNA表达水平与B7家族CD274、C10orf54、PDCD1LG2、ICOSLG和CD276相关；HCC组织中HHLA2的表达水平与肿瘤大小显著相关（χ2=4.531，P<0.05）；HHLA2低表达的HCC患者OS较HHLA2高表达患者显著延长（HR=1.878，95%CI：1.066~3.309，P<0.05）；多因素风险比例模型显示，肿瘤大小（HR=2.493，95%CI: 1.310~4.742，P<0.01）可作为HCC患者预后评估的独立危险因素。结论：HHLA2表达与HCC患者预后显著相关，是HCC免疫治疗的潜在新靶点。

Objective: To investigate the expression of human endogenous retrovirus subfamily H long terminal repeat associating protein 2 (HHLA2) in hepatocellular carcinoma (HCC) tissues and its correlation with the clinicopathological characteristics and prognosis of patients with HCC. Methods: Based on TCGA database, the correlation between HHLA2 mRNA expression and B7 family genes in human HCC tissues was analyzed. HHLA2 expression in 90 pairs of HCC tissues and their adjacent tissues was detected by tissue microarry and immunohistochemical staining. Wilcoxon rank sum test was used to compare the difference of HHLA2 expression between HCC tissues and its adjacent tissues. The chi-square test was used to analyze the relationship between HHLA2 expression in human HCC tissues and clinicopathological features of the patients. Kaplan-Meier survival analysis was performed to analyze the correlation between HHLA2 expression and patients’overall survival (OS), and the Cox model was used to evaluate the prognostic value of different indices. Results: The expression level of HHLA2 mRNA in HCC tissues was correlated with B7 family CD274, C10orf54, PDCD1LG2, ICOSLG and CD276. The expression level of HHLA2 in HCC tissues was significantly correlated with tumor size (χ2=4.531, P<0.05). The OS of HCC patients with high HHLA2 expression was significantly shorter than that of the patients with lower HHLA2 expression (HR=1.878, 95%CI: 1.066-3.309, P<0.05). The COX model showed that tumor size (HR=2.493,95%CI: 1.310-4.742, P<0.01) could be used as an independent risk factor for the prognostic prediction of the patients. Conclusion:HHLA2 is significantly correlated with the prognosis of HCC patients, and can be used as a potential target for HCC immunotherapy.

国家重点研发项目资助（No. 2018YFC1313400）；国家科技支撑计划资助项目（No. 2015BAI12B12）；国家自然科学基金海外及港澳学者合作研究基金项目（No. 31729001）；国家自然科学基金资助项目（No. 31570877, No. 81972869）；江苏省重点研发计划专项资金项目（No.BE2018645）