摘要
      肝细胞癌（HCC）由于预后差和治疗效果有限而被认为是一种致命的疾病。自噬在HCC中的作用以及自噬与肿瘤免疫微环境之间的关系越来越受到关注。因此，我们使用从TCGA数据集收集的基因表达谱，为HCC患者开发了一种新的基于自噬相关基因（ARGs）的预后风险特征。这种基于2-ARG的特征（BIRC5和SNRPB）在ICGC和GSE14520数据集中得到了验证，在总生存率和无复发生存率方面都取得了良好的性能。此外，在三个独立数据集中调整临床病理指标后，自噬基因特征可以独立预测HCC的总生存率。建立了包括自噬基因特征和TNM分期的列线图，为临床实践服务。值得注意的是，不同风险组的免疫细胞丰度不同，自噬高危组的关键免疫检查点和免疫抑制细胞因子上调。此外，通过蛋白质印迹在细胞系中和通过免疫组织化学在组织样品中验证了由BIRC5和SNRPB编码的蛋白质的表达水平。总之，基于2-ARG的预后风险特征可能是识别风险亚组、评估免疫微环境和为HCC患者提供治疗靶点的有用工具。
Abstract
Hepatocellular carcinoma (HCC) is considered a lethal disease due to the poor prognosis and the limited therapeutic efficacy. Much more attention is being attached to the role of autophagy in HCC, and the relationship between autophagy and tumor immune microenvironment. Therefore, we developed a novel prognostic risk signature based on autophagy-related genes (ARGs) for HCC patients using gene expression profiles collected from TCGA dataset. This 2-ARG-based signature (BIRC5 and SNRPB) was validated in ICGC and GSE14520 datasets, achieving a favorable performance in both overall survival and recurrence-free survival outcomes. Additionally, the autophagy gene signature could independently predict overall survival of HCC after adjusting clinicopathological indicators in three independent datasets. A nomogram including autophagy gene signature and TNM stage was built to serve clinical practice. Significantly, differential abundance of immune cells was shown in different risk groups and the critical immune checkpoints and immunosuppressive cytokines were upregulated in the autophagy high-risk group. Furthermore, the expression levels of proteins encoded by BIRC5 and SNRPB were validated in cell lines by western blot and in tissue samples by immunohistochemistry. In summary, the 2-ARG-based prognostic risk signature could be a useful tool to identify risk subgroups, evaluate immune microenvironment and provide therapeutic targets for HCC patients.

https://www.sciencedirect.com/science/article/pii/S0010482522011453