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基于胃腺癌特征和肿瘤免疫微环境,利用综合生物信息学分析对抗肿瘤药物靶点预测免疫原性细胞死亡相关lncRNA模型的预后价值。

Prognostic value of antitumor drug targets prediction using integrated bioinformatic analysis for immunogenic cell death-related lncRNA model based on stomach adenocarcinoma characteristics and tumor immune microenvironment.

作者信息

Ding Dayong, Zhao Yan, Su Yanzhuo, Yang Huaixi, Wang Xuefeng, Chen Lin

机构信息

Department of Gastrointestinal and Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.

Department of Operating Room, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.

出版信息

Front Pharmacol. 2022 Oct 14;13:1022294. doi: 10.3389/fphar.2022.1022294. eCollection 2022.

DOI:10.3389/fphar.2022.1022294
PMID:36313374
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9614277/
Abstract

Stomach adenocarcinoma (STAD) ranks as the fourth prevalent cause of mortality worldwide due to cancer. The prognosis for those suffering from STAD was bleak. Immunogenic cell death (ICD), a form of induced cellular death that causes an adaptive immune response and has increasing in anticancer treatment. However, it has not been ascertained how ICD-related lncRNAs affect STAD. Using univariate Cox regression and the TCGA database, lncRNAs with prognostic value were identified. Thereafter, we created a prognostic lncRNA-based model using LASSO. Kaplan-Meier assessment, time-dependent receiver operating characteristic (ROC) analyzation, independent prognostic investigation, and nomogram were used to assess model correctness. Additional research included evaluations of the immunological microenvironment, gene set enrichment analyses (GSEA), tumor mutation burdens (TMBs), tumor immune dysfunctions and exclusions (TIDEs), and antitumor compounds IC50 predictions. We found 24 ICD-related lncRNAs with prognostic value univariate Cox analysis ( < 0.05). Subsequently, a risk model was proposed using five lncRNAs relevant to ICD. The risk signature, correlated with immune cell infiltration, had strong predictive performance. Individuals at low-risk group outlived those at high risk ( < 0.001). An evaluation of the 5-lncRNA risk mode including ROC curves, nomograms, and correction curves confirmed its predictive capability. The findings of functional tests revealed a substantial alteration in immunological conditions and the IC50 sensitivity for the two groups. Using five ICD-related lncRNAs, the authors developed a new risk model for STAD patients that could predict their cumulative overall survival rate and guide their individual treatment.

摘要

胃腺癌(STAD)是全球癌症致死的第四大常见原因。STAD患者的预后不容乐观。免疫原性细胞死亡(ICD)是一种诱导性细胞死亡形式,可引发适应性免疫反应,在抗癌治疗中的应用日益广泛。然而,ICD相关的长链非编码RNA(lncRNAs)如何影响STAD尚未明确。利用单变量Cox回归和TCGA数据库,鉴定出具有预后价值的lncRNAs。此后,我们使用LASSO构建了基于lncRNA的预后模型。采用Kaplan-Meier评估、时间依赖性受试者工作特征(ROC)分析、独立预后研究和列线图来评估模型的准确性。其他研究包括免疫微环境评估、基因集富集分析(GSEA)、肿瘤突变负担(TMBs)、肿瘤免疫功能障碍和排除(TIDEs)以及抗肿瘤化合物IC50预测。通过单变量Cox分析(<0.05),我们发现了24个具有预后价值的ICD相关lncRNAs。随后,利用与ICD相关的5个lncRNAs建立了风险模型。该风险特征与免疫细胞浸润相关,具有很强的预测性能。低风险组个体的生存期长于高风险组(<0.001)。对包括ROC曲线、列线图和校正曲线在内的5-lncRNA风险模型的评估证实了其预测能力。功能测试结果显示两组免疫状态和IC50敏感性存在显著差异。作者利用5个与ICD相关的lncRNAs为STAD患者开发了一种新的风险模型,该模型可以预测患者的累积总生存率并指导个体化治疗。

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