Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, No.2 fuxue lane, Wenzhou, Zhejiang, P.R. China.
BMC Cancer. 2023 Oct 24;23(1):1029. doi: 10.1186/s12885-023-11521-x.
Necroptosis has been reported to be involved in cancer progression and associated with cancer prognosis. However, the prognostic values of necroptosis-related genes (NRGs) in hepatocellular carcinoma (HCC) remain largely unknown. This study aimed to build a signature on the basis of NRGs to evaluate the prognosis of HCC patients. In this study, using bioinformatic analyses of transcriptome sequencing data of HCC (n = 370) from The Cancer Genome Atlas (TCGA) database, 63 differentially expressed NRGs between HCC and adjacent normal tissues were determined. 24 differentially expressed NRGs were found to be related with overall survival (OS). Seven optimum NRGs, determined using Lasso regression and multivariate Cox regression analysis, were used to construct a new prognostic risk signature for predicting the prognosis of HCC patients. Then survival status scatter plots and survival curves demonstrated that the prognosis of patients with high-Riskscore was worse. The prognostic value of this 7-NRG signature was validated by the International Cancer Genome Consortium (ICGC) cohort and a local cohort (Wenzhou, China). Notably, Riskscore was defined as an independent risk factor for HCC prognosis using multivariate cox regression analysis. Immune infiltration analysis suggested that higher macrophage infiltration was found in patients in the high-risk group. Finally, enhanced 7 NRGs were found in HCC tissues by immunohistochemistry. In conclusion, a novel 7-NRG prognostic risk signature is generated, which contributes to the prediction in the prognosis of HCC patients for the clinicians.
细胞坏死已被报道参与癌症的进展，并与癌症的预后相关。然而，细胞坏死相关基因（NRGs）在肝细胞癌（HCC）中的预后价值在很大程度上仍然未知。本研究旨在基于 NRGs 构建一个signature，以评估 HCC 患者的预后。
在这项研究中，我们使用转录组测序数据的生物信息学分析，对来自癌症基因组图谱（TCGA）数据库的 HCC（n=370）进行分析，确定了 63 个 HCC 与邻近正常组织之间差异表达的 NRGs。发现 24 个差异表达的 NRGs与总生存期（OS）相关。通过 Lasso 回归和多变量 Cox 回归分析确定了 7 个最优 NRGs，用于构建预测 HCC 患者预后的新的预后风险 signature。然后生存状态散点图和生存曲线表明高风险评分患者的预后较差。该 7-NRG 签名的预后价值通过国际癌症基因组联盟（ICGC）队列和本地队列（中国温州）进行了验证。值得注意的是，多变量 Cox 回归分析定义 Riskscore 是 HCC 预后的独立危险因素。免疫浸润分析表明，高风险组患者的巨噬细胞浸润较高。最后，通过免疫组织化学发现 HCC 组织中增强了 7 个 NRGs。
总之，我们生成了一个新的 7-NRG 预后风险 signature，可以为临床医生预测 HCC 患者的预后提供帮助。
