研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

G0 停滞基因模式预测肺腺癌患者的预后和药物敏感性。

G0 arrest gene patterns to predict the prognosis and drug sensitivity of patients with lung adenocarcinoma.

发表日期:2024
作者: Yong Ma, Zhilong Li, Dongbing Li, Baozhen Zheng, Yanfeng Xue
来源: GENES & DEVELOPMENT

摘要:

G0停滞(G0A)被广泛认为是导致肿瘤复发的关键因素。 G0A 相关基因在肺腺癌 (LUAD) 中的作用尚不清楚。本研究旨在开发基于 LUAD 患者的基因特征,并研究其与 LUAD 预后、肿瘤免疫微环境和治疗反应的关系。我们使用 TCGA-LUAD 数据库作为发现队列,特别关注与 G0A 途径相关的基因。我们使用了各种统计方法(包括 Cox 和 lasso 回归)来开发模型。我们使用批量转录组和单细胞转录组数据集(GSE50081、GSE72094、GSE127465、GSE131907 和 EMTAB6149)验证了模型。我们使用 GSEA 富集和 CIBERSORT 算法来深入了解信号通路的注释和肿瘤微环境的表征。我们评估了这些患者对免疫治疗、化疗和靶向治疗的反应。通过定量实时 PCR (qRT-PCR) 验证了细胞系中六个基因的表达。我们的研究成功建立了六基因特征(CHCHD4、DUT、LARP1、PTTG1IP、RBM14 和 WBP11),该特征对 LUAD 患者的总生存期具有显着的预测能力。它证明了 LUAD 的独立预后价值。为了增强临床适用性,我们根据该基因特征开发了列线图,该列线图在预测患者结果方面表现出高度可靠性。此外,我们观察到 G0A 相关风险与肿瘤微环境以及药物敏感性之间存在显着关联,凸显了基因特征指导个性化治疗策略的潜力。 LUAD 细胞系中六个基因的表达显着上调。这一特征有可能有助于改善预后预测和专门针对 LUAD 患者的新的个性化治疗。版权所有:© 2024 Ma 等人。这是一篇根据知识共享署名许可条款分发的开放获取文章,允许在任何媒体上不受限制地使用、分发和复制,前提是注明原始作者和来源。
G0 arrest (G0A) is widely recognized as a crucial factor contributing to tumor relapse. The role of genes related to G0A in lung adenocarcinoma (LUAD) was unclear. This study aimed to develop a gene signature based on for LUAD patients and investigate its relationship with prognosis, tumor immune microenvironment, and therapeutic response in LUAD. We use the TCGA-LUAD database as the discovery cohort, focusing specifically on genes associated with the G0A pathway. We used various statistical methods, including Cox and lasso regression, to develop the model. We validated the model using bulk transcriptome and single-cell transcriptome datasets (GSE50081, GSE72094, GSE127465, GSE131907 and EMTAB6149). We used GSEA enrichment and the CIBERSORT algorithm to gain insight into the annotation of the signaling pathway and the characterization of the tumor microenvironment. We evaluated the response to immunotherapy, chemotherapy, and targeted therapy in these patients. The expression of six genes was validated in cell lines by quantitative real-time PCR (qRT-PCR). Our study successfully established a six-gene signature (CHCHD4, DUT, LARP1, PTTG1IP, RBM14, and WBP11) that demonstrated significant predictive power for overall survival in patients with LUAD. It demonstrated independent prognostic value in LUAD. To enhance clinical applicability, we developed a nomogram based on this gene signature, which showed high reliability in predicting patient outcomes. Furthermore, we observed a significant association between G0A-related risk and tumor microenvironment as well as drug susceptibility, highlighting the potential of the gene signature to guide personalized treatment strategies. The expression of six genes were significantly upregulated in the LUAD cell lines. This signature holds the potential to contribute to improved prognostic prediction and new personalized therapies specifically for LUAD patients.Copyright: © 2024 Ma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.