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Identification and validation of a five-necroptosis-related lncRNAs signature for prognostic prediction in hepatocellular carcinoma

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机构: [1]Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China [2]Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital, Southwest Medical University, Metabolic Hepatobiliary and Pancreatic Diseases Key Laboratory of Luzhou City, Luzhou, 646000, China [3]Department of Hepato-Biliary-Pancreatic Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610041, China
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关键词: Necroptosis Hepatocellular carcinoma Long non-coding RNAs Prognostic signature Bioinformation

摘要:
Background: Hepatocellular carcinoma (HCC) is among the most prevalent digestive system malignancies and is associated with a poor prognosis. Necroptosis, a form of regulated death mediated by death receptors, exhibits characteristics of both necrosis and apoptosis. Long noncoding RNAs (lncRNAs) have been identified as crucial regulators in tumor necroptosis. This study aims to identify the necroptosis-related lncRNAs (np-lncRNA) in HCC and investigate their relationships with prognosis. Method: The RNA-sequencing data, along with clinicopathological and survival information of HCC patients were sourced from The Cancer Genome Atlas (TCGA) database. The np-lncRNAs were analyzed to assess their potential in predicting HCC prognosis. Prognostic signatures related to necroptosis were constructed using stepwise multivariate Cox regression analysis. The prognosis of patients was compared using Kaplan-Meier (KM) analysis. The accuracy of the prognostic signature was evaluated using Receiver operating characteristic (ROC) analysis and decision curve analysis (DCA). Quantitative real-time polymerase chain reaction(qPCR) was employed to validate the lncRNAs expression levels of lncRNAs among samples from an independent cohort. Results: The np-lncRNAs ZFPM2-AS1, AC099850.3, BACE1-AS, KDM4A-AS1 and MKLN1-AS were identified as potential prognostic biomarkers. The prognostic signature constructed from these np-lncRNAs achieved an Area Under the Curve (AUC) of 0.773. Based on the risk score derived from the signature, patients were divided into two groups, with the high-risk group exhibiting poorer overall survival. Gene Set Enrichment Analysis (GSEA) revealed significantly different between the low risk and high risk groups in tumor-related pathways (such as mTOR, MAPK and p53 signaling pathways) and immune-related functions (like T cell receptor signaling pathway and natural killer cell mediated cytotoxicity). The increased expression of np-lncRNAs was confirmed in another independent HCC cohort. Conclusions: This signature offers a dependable method for forecasting the prognosis of HCC patients. Our findings indicate a subset of np-lncRNA biomarkers that could be utilized for prognosis prediction and personalized treatment strategies of HCC patients.

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大类 | 3 区 综合性期刊
小类 | 3 区 综合性期刊
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Q1 MULTIDISCIPLINARY SCIENCES

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第一作者机构: [1]Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China [2]Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital, Southwest Medical University, Metabolic Hepatobiliary and Pancreatic Diseases Key Laboratory of Luzhou City, Luzhou, 646000, China
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