| 张玉俊,朱琳,赵璇,等.基于坏死性凋亡相关长链非编码 RNA构建肝细胞癌预后模型及药物治疗反应分析[J].安徽医药,2023,27(8):1595-1601. |
| 基于坏死性凋亡相关长链非编码 RNA构建肝细胞癌预后模型及药物治疗反应分析 |
| Prognostic model construction and drugtherapy response analysis of hepatocellular carcino ma based on necroptosis-related long noncoding RNA |
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| DOI：10.3969/j.issn.1009-6469.2023.08.023 |
| 中文关键词: 癌，肝细胞 坏死性凋亡 长链非编码 RNA 肿瘤免疫微环境 总生存期 |
| 英文关键词: Carcinoma,hepatocellular Necroptosis LncRNA Tumor immune microenvironment Overall survival |
| 基金项目:新疆维吾尔自治区自然科学基金项目( 2021D01C379)；省部共建中亚高发病成因与防治国家重点实验室开放课题项目( SKL-HIDCA-2020-ER3，SKL-HIDCA-2020-33) |
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| 中文摘要: |
| 目的使用坏死性凋亡相关长链非编码 RNA(NRLs)构建肝细胞癌( HCC)预后模型并分析不同风险组间药物敏感性差异，为 HCC病人预后预测和临床个体化治疗提供理论依据。方法从癌症基因组图谱( TCGA)数据库中下载 HCC病人的 RNA测序数据和临床信息。采用共表达网络分析鉴定 NRLs。使用单变量 Cox回归和 LASSO-Cox回归构建预后模型，并在测试集和整个集合中进行验证。运用生存分析、受试者操作特征( ROC)曲线、临床病理分层相关性分析、多变量 Cox回归、列线图和校准曲线来评估预后模型。随后，采用基因集富集分析( GSEA)不同风险群体间生物过程和功能的差异。使用单样本基因集富集分析( ssGSEA)来探讨不同风险群体与肿瘤免疫、浸润之间的关系，并采用 Pearson相关分析 HCC病人预后特征与免疫检查点表达的相关性。最后，使用药物敏感性分析 20种化疗药物在不同风险群体中的 IC50值。结果构建了由 4个 NRLs |
| 英文摘要: |
| Objective To construct a prognostic model of hepatocellular carcinoma (HCC) using necroptosis-related long noncodingRNAs (NRLS) and analyze the difference of drug sensitivity among different risk groups, so as to provide a theoretical basis for prognosis prediction and clinical individualized treatment of HCC patients.Methods RNA sequencing data and clinical information of HCCpatients were downloaded from the cancer genome atlas (TCGA) database. NRLS were identified by co-expression network analysis. Aprognostic model was constructed using univariate Cox regression and lasso Cox regression and validated in the test set and whole set.Survival analysis, receiver operating characteristic curve (ROC), stratified correlation analysis with clinicopathology, multivariate Coxregression, nomogram and calibration curve were used to evaluate the prognostic model. Subsequently, gene set enrichment analysis(GSEA) was employed to investigate the differences in biological processes and functions among different risk groups. Single samplegene set enrichment analysis (ssGSEA) was used to explore the relationship between different risk groups and the tumor microenvironment, and Pearson correlation was employed to analyze the correlation between predictive features and immune checkpoint expression in HCC patients. Finally, the IC50 values of 20 chemotherapeutic agents in different risk groups were analyzed using drug sensitivity.Results A risk score (NRLS risk-score) prognostic signature consisting of four NRLS (ZFPM2-AS1, MKLN1-AS, LINC01116, AP003390.1) was constructed, and patients were assigned into high -and low-risk groups according to the median risk score values. Survival analysis showed that the overall survival (OS) of the low-risk group with NRLS was significantly longer than that of the high-risk group. Compared with clinicopathological variables, the NRLS risk score signature had higher diagnostic efficiency with an area under the receiver operating characteristic curve (AUC) of 0.74. Survival analysis stratified by clinicopathological variables showed thatOS of patients in the high-risk group was significantly lower than that in the low-risk group. Multivariate Cox results showed that stage and NRLS risk-score could serve as independent prognostic factors for HCC patients, and the combination of clinicopathological features and NRLS risk-score histogram showed good predictive performance. GSEA analysis indicated that cancer-related pathways were mainly enriched in the high-risk group. The ssGSEA results showed that the NRLS predictive signature was significantly associatedwith the immune status of HCC patients. The results of immune checkpoint analysis showed that the expression of immune checkpointsin patients with high-risk group was higher, indicating that the immune function of HCC patients in high-risk group who may benefitfrom checkpoint blocker immunotherapy was more active. The results of drug sensitivity analysis showed that the IC50 values of 16 chemotherapeutic drugs differed between high and low risk groups.Conclusion The risk characteristics of the 4 NRLS are helpful to evaluate the prognosis and molecular characteristics of HCC patients, which can be used to further optimize the personalized treatment andmanagement strategies of HCC. |
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