Department of Gastroenterology, Jiangxi Clinical Research Center for Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, China.
Sci Rep. 2022 Dec 26;12(1):22355. doi: 10.1038/s41598-022-26795-7.
Due to the high mortality of hepatocellular carcinoma (HCC), its prognostic models are urgently needed. Bile acid (BA) metabolic disturbance participates in hepatocarcinogenesis. We aim to develop a BA-related gene signature for HCC patients. Research data of HCC were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) online databases. After least absolute shrinkage and selection operator (LASSO) regression analysis, we developed a BA-related prognostic signature in TCGA cohort based on differentially expressed prognostic BA-related genes. Then, the predictive performance of the signature was evaluated and verified in TCGA and ICGC cohort respectively. We obtained the risk score of each HCC patient according to the model. The differences of immune status and drug sensitivity were compared in patients that were stratified based on risk score. The protein and mRNA levels of the modeling genes were validated in the Human Protein Atlas database and our cell lines, respectively. In TCGA cohort, we selected 4 BA-related genes to construct the first BA-related prognostic signature. The risk signature exhibited good discrimination and predictive ability, which was verified in ICGC cohort. Patients were classified into high- and low-risk groups according to their median scores. The occurrence of death increased with increasing risk score. Low-risk patients owned favorable overall survival. High-risk patients possessed high immune checkpoint expression and low IC50 values for sorafenib, cisplatin and doxorubicin. Real-time quantitative PCR and immunohistochemical results validate expression of modeling genes in the signature. We constructed the first BA-related gene signature, which might help to identify HCC patients with poor prognosis and guide individualized treatment.
由于肝细胞癌 (HCC) 的死亡率很高，因此迫切需要其预后模型。胆汁酸 (BA) 代谢紊乱参与肝癌的发生。我们旨在为 HCC 患者开发一个与 BA 相关的基因特征。HCC 的研究数据来自癌症基因组图谱 (TCGA) 和国际癌症基因组联盟 (ICGC) 在线数据库。经过最小绝对值收缩和选择算子 (LASSO) 回归分析，我们在 TCGA 队列中基于差异表达的与预后相关的 BA 相关基因开发了一个与 BA 相关的预后特征。然后，分别在 TCGA 和 ICGC 队列中评估和验证特征的预测性能。我们根据模型为每个 HCC 患者获得风险评分。根据风险评分对患者进行分层，比较免疫状态和药物敏感性的差异。在人类蛋白质图谱数据库和我们的细胞系中分别验证了建模基因的蛋白和 mRNA 水平。在 TCGA 队列中，我们选择了 4 个与 BA 相关的基因来构建第一个与 BA 相关的预后特征。风险特征显示出良好的区分和预测能力，在 ICGC 队列中得到了验证。根据中位数评分，患者被分为高风险和低风险组。死亡的发生随着风险评分的增加而增加。低风险患者的总体生存率较好。高风险患者具有高免疫检查点表达和低索拉非尼、顺铂和阿霉素的 IC50 值。实时定量 PCR 和免疫组织化学结果验证了特征中建模基因的表达。我们构建了第一个与 BA 相关的基因特征，这可能有助于识别预后不良的 HCC 患者，并指导个体化治疗。
