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构建新型 MPT 驱动的坏死相关 lncRNAs 标志物用于预测喉鳞状细胞癌的预后。

Construction of a novel MPT-driven necrosis-related lncRNAs signature for prognosis prediction in laryngeal squamous cell carcinoma.

机构信息

Department of Otolaryngology-Head and Neck Surgery, QingPu Branch of Zhongshan Affilated to Fudan University, Shanghai, 201700, People's Republic of China.

Xiangya Hospital, Central South University, Changsha, Hunan, 41000, People's Republic of China.

出版信息

Environ Sci Pollut Res Int. 2023 Jul;30(31):77210-77225. doi: 10.1007/s11356-023-26996-1. Epub 2023 May 30.

Abstract

Mitochondrial permeability transition (MPT)-driven necrosis, a type of programmed cell death, has recently gained much attention in a variety of tumor types. Few studies have been performed to explore the role of MPT-driven necrosis-related lncRNAs (MPTDNRlncRNAs) in laryngeal squamous cell carcinoma (LSCC). The purpose of our study is to screen MPTDNRlncRNAs with prognostic value and to explore their potential roles in LSCC. The RNA-sequencing data and the corresponding clinical data of LSCC patients were obtained from the TCGA database, and those MPT-driven necrosis-related genes were extracted from the Gene Set Enrichment Analysis (GSEA) database. We identified MPTDNRlncRNAs differentially expressed in LSCC. Also, we gained MPT-driven necrosis-related prognostic lncRNAs by univariate cox regression analysis. A novel MPTDNRlncRNAs signature was constructed by LASSO-COX. The accuracy and utility of the MPTDNRlncRNAs signature were evaluated via a variety of statistical methods. Multiple bioinformatics tools were used to explore the underlying difference in biological functions and signaling pathways between the different risk groups. The expressions levels of MPTDNRlncRNAs were analyzed using RT-qPCR in LSCC cell line. Finally, we identified A 5 MPTDNRlncRNAs signature in LSCC. Our prognostic model demonstrated an efficient ability to predict outcomes. The proportion difference of immune cells in the subgroups were significant, such as M0 macrophage and T follicular helper cells. The in vitro experiments suggested that our MPTDNRlncRNAs were significantly different. This 5 MPTDNRlncRNAs signature is a prognostic biomarker for LSCC. More importantly, the novel biologic prognostic model can be utilized for personalized immunotherapy in LSCC patients.

摘要

线粒体通透性转换(MPT)驱动的坏死是一种程序性细胞死亡,最近在多种肿瘤类型中引起了广泛关注。很少有研究探讨 MPT 驱动的坏死相关长非编码 RNA(MPTDNRlncRNAs)在喉鳞状细胞癌(LSCC)中的作用。我们的研究目的是筛选具有预后价值的 MPTDNRlncRNAs,并探讨它们在 LSCC 中的潜在作用。我们从 TCGA 数据库中获得了 LSCC 患者的 RNA 测序数据和相应的临床数据,并从基因集富集分析(GSEA)数据库中提取了与 MPT 驱动的坏死相关的基因。我们鉴定了 LSCC 中差异表达的 MPTDNRlncRNAs。此外,我们通过单因素 cox 回归分析获得了与 MPT 驱动的坏死相关的预后 lncRNAs。通过 LASSO-COX 构建了一个新的 MPTDNRlncRNAs 特征。通过多种统计方法评估了 MPTDNRlncRNAs 特征的准确性和实用性。使用多种生物信息学工具来探讨不同风险组之间生物学功能和信号通路的潜在差异。使用 RT-qPCR 分析了 LSCC 细胞系中 MPTDNRlncRNAs 的表达水平。最后,我们在 LSCC 中确定了一个由 5 个 MPTDNRlncRNAs 组成的特征。我们的预后模型能够有效地预测结局。亚组之间免疫细胞的比例差异显著,如 M0 巨噬细胞和滤泡辅助 T 细胞。体外实验表明,我们的 MPTDNRlncRNAs 有显著差异。这个由 5 个 MPTDNRlncRNAs 组成的特征是 LSCC 的一个预后生物标志物。更重要的是,新的生物预后模型可以用于 LSCC 患者的个性化免疫治疗。

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