代谢产物是癌症的重要指标，与氨基酸代谢相关基因的突变可能影响肿瘤发生。免疫疗法是一种有效的癌症治疗选择，然而其与氨基酸代谢的关系尚未报告。本研究从TCGA获取了371例肝癌患者的RNA-seq数据，作为训练集，从ICGC获得了231例肝癌患者的数据作为验证集，建立了基于基因签名的肝癌整体生存和免疫治疗反应的预测模型。通过对371例肝癌患者的132个与氨基酸代谢相关的差异表达基因进行一致性聚类，得到了4个可靠的分组，开发了一个四基因签名用于预测肝癌生存结局。我们的数据显示，在不同的临床组中，高风险组的总体生存结局明显较低。单变量和多变量分析表明，这四个基因的特征是肝癌独立的预后因素。ROC曲线显示风险特征是1年、2年和3年HCC生存结局的有效预测因子。GSVA和KEGG通路分析表明，高风险评分肿瘤与肝癌恶性程度的各个方面相关。高风险组中的突变基因更多，免疫渗透更大。对三个免疫治疗组的评估表明，低风险评分的患者在免疫治疗中显著受益。然后，我们基于TCGA队列建立了一个预后评分表。总的来说，这四个基因的签名是一个可靠的诊断标记和免疫治疗效果的预测因子。©2023. 该作者，独家授权给Springer Science + Business Media, LLC，Springer Nature的一部分。

Metabolites are important indicators of cancer and mutations in genes involved in amino acid metabolism may influence tumorigenesis. Immunotherapy is an effective cancer treatment option; however, its relationship with amino acid metabolism has not been reported. In this study, RNA-seq data for 371 liver cancer patients were acquired from TCGA and used as the training set. Data for 231 liver cancer patients were obtained from ICGC and used as the validation set to establish a gene signature for predicting liver cancer overall survival outcomes and immunotherapeutic responses. Four reliable groups based on 132 amino acid metabolism-related DEGs were obtained by consistent clustering of 371 HCC patients and a four-gene signature for prediction of liver cancer survival outcomes was developed. Our data show that in different clinical groups, the overall survival outcomes in the high-risk group were markedly low relative to the low-risk group. Univariate and multivariate analyses revealed that the characteristics of the 4-gene signature were independent prognostic factors for liver cancer. The ROC curve revealed that the risk characteristic is an efficient predictor for 1-, 2-, and 3-year HCC survival outcomes. The GSVA and KEGG pathway analyses revealed that high-risk score tumors were associated with all aspects of the degree of malignancy in liver cancer. There were more mutant genes and greater immune infiltrations in the high-risk groups. Assessment of the three immunotherapeutic cohorts established that low-risk score patients significantly benefited from immunotherapy. Then, we established a prognostic nomogram based on the TCGA cohort. In conclusion, the 4-gene signature is a reliable diagnostic marker and predictor for immunotherapeutic efficacy.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.