Abstract: Objective To analyze the expression, prognostic and immune infiltrationroles of FAM72 gene family （FAM72s） in hepatocellular carcinoma （HCC）. Methods TCGA was used to analyze the expression of FAM72s in patients with HCC, the differences among different clinical characteristics, and independentprognostic values. The relationships of FAM72s expression and overall survival （OS） were assessed using TCGA and Kaplan-Meier plotter. STRING was used to detect the protein-proteininteraction （PPI） networks forFAM72s. The relationship of FAM72s expression and immune infiltration was performed by the ssGSEA. We used GEPIA to evaluate the correlation of FAM72s expression with biomarkers of immune cells and immune checkpoints in HCC. Results The expressions of FAM72A-D in HCC were significantly increased compared with those in normal liver tissues （P<0.05）. The OS in the high FAM72A-D expression group were shorter than those in the low expression group （P<0.05）. Univariate/multivariate regression analysisand ROC curve indicated that FAM72A-D could be used as an independent risk factor affecting the prognosis of HCC patients （P<0.05）. PPI networks showed that FAM72A-D compared with various proteinsparticipated in the progression of HCC. The results of immune infiltration analysis showed that the expression level of FAM72A-D was significantly correlated with the levels of mostinfiltrating immune cells and various biomarkers of immune cells. PD-1, PD-L1, and CTLA-4 levels were positively correlated with FAM72A-D expression. Conclusions FAM72s were highly expressed in HCC tissues and were associated with immune infiltration and poor prognosis. FAM72s may be significant biomarkers of HCC.

Key words: hepatocellular carcinoma, FAM72 gene family, prognosis, immune infiltration, bioinformatics analysis

摘要： 目的 探讨FAM72基因家族在肝细胞癌（HCC）中的表达情况及其与预后、免疫浸润的相关性。方法 应用TCGA分析FAM72基因家族在HCC中的表达情况、与不同临床特征间的差异及其预后价值;TCGA和Kaplan-Meier plotter分析FAM72基因家族对HCC患者总生存期的影响;STRING构建FAM72基因家族蛋白相互作用网络;ssGSEA分析FAM72基因家族与免疫浸润细胞间的相关性;GEPIA分析FAM72基因家族与免疫细胞分子标志物及免疫检查点的相关性。结果 HCC中FAM72-D的表达量显著高于正常肝组织（P<0.05）。FAM72A-D高表达组患者总生存率显著低于低表达组（P<0.05）。单因素/多因素回归分析和ROC曲线提示FAM72A-D可以作为影响HCC患者预后的独立危险因素（P<0.05）。蛋白互作网络分析结果提示FAM72A-D与多种蛋白一起参与HCC的发生发展。免疫浸润分析结果显示FAM72A-D表达水平与多数免疫细胞浸润水平及免疫细胞分子标志物有关,且与免疫检查点（PD-1、PD-L1、CTLA-4）有正相关关系。结论 FAM72基因家族在HCC组织中高表达,并与免疫浸润、不良预后相关,可作为HCC预后的预测指标。

关键词: 肝细胞癌, FAM72基因家族, 预后, 免疫浸润, 生物信息学分析