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一种基于细胞凋亡的基因签名,用于预测恶性胸膜间皮瘤的预后并揭示免疫浸润。

An anoikis-based gene signature for predicting prognosis in malignant pleural mesothelioma and revealing immune infiltration.

机构信息

Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang District, Harbin, 150081, Heilongjiang, People's Republic of China.

出版信息

J Cancer Res Clin Oncol. 2023 Oct;149(13):12089-12102. doi: 10.1007/s00432-023-05128-9. Epub 2023 Jul 8.

Abstract

INTRODUCTION

Malignant pleural mesothelioma (MPM) is an aggressive, treatment-resistant tumor. Anoikis is a particular type of programmed apoptosis brought on by the separation of cell-cell or extracellular matrix (ECM). Anoikis has been recognized as a crucial element in the development of tumors. However, few studies have comprehensively examined the role of anoikis-related genes (ARGs) in malignant mesothelioma.

METHODS

ARGs were gathered from the GeneCard database and the Harmonizome portals. We obtained differentially expressed genes (DEGs) using the GEO database. Univariate Cox regression analysis, and the least absolute shrinkage and selection operator (LASSO) algorithm were utilized to select ARGs associated with the prognosis of MPM. We then developed a risk model, and time-dependent receiver operating characteristic (ROC) analysis and calibration curves were employed to confirm the ability of the model. The patients were divided into various subgroups using consensus clustering analysis. Based on the median risk score, patients were divided into low- and high-risk groups. Functional analysis and immune cell infiltration analysis were conducted to estimate molecular mechanisms and the immune infiltration landscape of patients. Finally, drug sensitivity analysis and tumor microenvironment landscape were further explored.

RESULTS

A novel risk model was constructed based on the six ARGs. The patients were successfully divided into two subgroups by consensus clustering analysis, with a striking difference in the prognosis and landscape of immune infiltration. The Kaplan-Meier survival analysis indicated that the OS rate of the low-risk group was significantly higher than the high-risk group. Functional analysis, immune cell infiltration analysis, and drug sensitivity analysis showed that high- and low-risk groups had different immune statuses and drug sensitivity.

CONCLUSIONS

In summary, we developed a novel risk model to predict MPM prognosis based on six selected ARGs, which could broaden comprehension of personalized and precise therapy approaches for MPM.

摘要

简介

恶性胸膜间皮瘤(MPM)是一种侵袭性、治疗抵抗性肿瘤。失巢凋亡是一种特定类型的程序性细胞凋亡,由细胞-细胞或细胞外基质(ECM)的分离引起。失巢凋亡已被认为是肿瘤发生的关键因素。然而,很少有研究全面检查与失巢凋亡相关的基因(ARGs)在恶性间皮瘤中的作用。

方法

ARGs 从 GeneCard 数据库和 Harmonizome 门户中收集。我们使用 GEO 数据库获得差异表达基因(DEGs)。单变量 Cox 回归分析和最小绝对值收缩和选择算子(LASSO)算法用于选择与 MPM 预后相关的 ARGs。然后我们开发了一个风险模型,并使用时间依赖性接收器操作特征(ROC)分析和校准曲线来确认模型的能力。使用共识聚类分析将患者分为不同的亚组。根据中位数风险评分,将患者分为低风险组和高风险组。进行功能分析和免疫细胞浸润分析,以评估患者的分子机制和免疫浸润景观。最后,进一步探索了药物敏感性分析和肿瘤微环境景观。

结果

基于六个 ARGs 构建了一个新的风险模型。通过共识聚类分析,患者成功地分为两个亚组,在预后和免疫浸润景观方面存在显著差异。Kaplan-Meier 生存分析表明,低风险组的 OS 率明显高于高风险组。功能分析、免疫细胞浸润分析和药物敏感性分析表明,高风险组和低风险组具有不同的免疫状态和药物敏感性。

结论

总之,我们基于六个选定的 ARGs 开发了一种新的风险模型来预测 MPM 的预后,这可以拓宽对 MPM 个性化和精确治疗方法的理解。

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