硒代谢调节剂相关预后模型在肝细胞癌中的建立和验证。
Development and validation of a selenium metabolism regulators associated prognostic model for hepatocellular carcinoma.
机构信息
Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
出版信息
BMC Cancer. 2023 May 18;23(1):451. doi: 10.1186/s12885-023-10944-w.
BACKGROUND
Selenium metabolism has been implicated in human health. This study aimed to identify a selenium metabolism regulator-based prognostic signature for hepatocellular carcinoma (HCC) and validate the role of INMT in HCC.
METHODS
Transcriptome sequencing data and clinical information related to selenium metabolism regulators in TCGA liver cancer dataset were analysed. Next, a selenium metabolism model was constructed by multiple machine learning algorithms, including univariate, least absolute shrinkage and selection operator, and multivariate Cox regression analyses. Then, the potential of this model for predicting the immune landscape of different risk groups was evaluated. Finally, INMT expression was examined in different datasets. After knockdown of INMT, cell proliferation and colony formation assays were conducted.
RESULTS
A selenium metabolism model containing INMT and SEPSECS was established and shown to be an independent predictor of prognosis. The survival time of low-risk patients was significantly longer than that of high-risk patients. These two groups had different immune environments. In different datasets, including TCGA, GEO, and our PUMCH dataset, INMT was significantly downregulated in HCC tissues. Moreover, knockdown of INMT significantly promoted HCC cell proliferation.
CONCLUSIONS
The current study established a risk signature of selenium metabolism regulators for predicting the prognosis of HCC patients. INMT was identified as a biomarker for poor prognosis of HCC.
背景
硒代谢与人类健康有关。本研究旨在鉴定基于硒代谢调节剂的肝细胞癌(HCC)预后特征,并验证 INMT 在 HCC 中的作用。
方法
分析 TCGA 肝癌数据集中转录组测序数据和与硒代谢调节剂相关的临床信息。接下来,通过多种机器学习算法(包括单变量、最小绝对值收缩和选择算子以及多变量 Cox 回归分析)构建硒代谢模型。然后,评估该模型预测不同风险组免疫景观的潜力。最后,在不同的数据集检查 INMT 的表达。敲低 INMT 后,进行细胞增殖和集落形成实验。
结果
建立了包含 INMT 和 SEPSECS 的硒代谢模型,并证实其是预后的独立预测因子。低风险患者的生存时间明显长于高风险患者。这两组的免疫环境不同。在 TCGA、GEO 和我们的 PUMCH 数据集等不同数据集,HCC 组织中 INMT 明显下调。此外,敲低 INMT 显著促进 HCC 细胞增殖。
结论
本研究建立了预测 HCC 患者预后的硒代谢调节剂风险特征。INMT 被鉴定为 HCC 预后不良的生物标志物。