Immune implication of FAM83D gene in hepatocellular carcinoma

FAM83D has been demonstrated to contribute to tumorigenesis. However, its immune effects in hepatocellular carcinoma (HCC) have not been reported. This study aimed to identify the immune role of FAM83D in HCC. FAM83D was over-expressed in HCC and contributed to poor prognosis according to the results of data analysis based on The Cancer Genome Atlas (TCGA). Afterward, the levels of immune cells infiltration were found to be correlated with the expression level of FAM83D in HCC. Through TISIDB and cBioPortal network tools, a total of 82 FAM83D-associated genes were screened out, including 12 immunoinhibitors, 20 immunostimulators and 50 tightly co-expressed genes. TCGA cohort was divided into train set and test set on the basis of the proportion of 7:3. According to FAM83D-associated immunomodulators, a four gene predicted model was established using train set via the Cox regression analysis. Survival analysis demonstrated that the overall survival (OS) of high-risk HCC patients was poor compared with the patients in low-risk group. The reliability and predicted power of the risk-score model were identified by a receiver operating characteristic (ROC) curve. A risk-score based nomogram as well as a calibration curve, which were created could be used to anticipate patient’s 1-year, 3-year and 5-year survival probabilities. The test set was used to validate these results. Our findings showed that the FAM83D gene was related with HCC immunity. The immune marker chosen could be a promising biomarker for HCC prognosis.

已有研究证实，FAM83D可促进肿瘤发生。然而其在肝细胞癌（hepatocellular carcinoma，HCC）中的免疫调控作用尚未见报道。本研究旨在阐明FAM83D在肝细胞癌中的免疫功能。基于癌症基因组图谱（The Cancer Genome Atlas，TCGA）的数据分析结果显示，FAM83D在肝细胞癌组织中呈高表达状态，且与患者不良预后显著相关。进一步分析发现，肝细胞癌组织中免疫细胞浸润水平与FAM83D的表达水平密切相关。通过TISIDB与cBioPortal两款网络工具，本研究共筛选得到82个与FAM83D相关的基因，其中包括12个免疫抑制因子、20个免疫刺激因子以及50个紧密共表达基因。本研究将TCGA队列按照7:3的比例划分为训练集与测试集。基于FAM83D相关免疫调节因子，本研究通过Cox回归分析，利用训练集构建了包含4个基因的预测模型。生存分析结果显示，高风险肝细胞癌患者的总生存期（overall survival，OS）显著差于低风险组患者。受试者工作特征（receiver operating characteristic，ROC）曲线分析证实了该风险评分模型的可靠性与预测效能。本研究构建了基于风险评分的列线图与校正曲线，可用于预测肝细胞癌患者1年、3年及5年的生存概率。本研究利用测试集对上述结果进行了验证。本研究结果证实，FAM83D基因与肝细胞癌的免疫进程密切相关，其所筛选得到的免疫标志物有望成为肝细胞癌预后评估的潜在生物标志物。