研究动态
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基于线粒体代谢相关基因的胰腺癌预后模型的建立

Establishment of a prognostic model for pancreatic cancer based on mitochondrial metabolism related genes.

发表日期:2024 Aug 28
作者: Qinwen Ba, Xiong Wang, Yanjun Lu
来源: Cellular & Molecular Immunology

摘要:

胰腺导管腺癌(PAAD)被认为是一种极具侵袭性的癌症,具有高度致命性且预后不良。线粒体代谢途径与肿瘤发生和肿瘤进展密切相关,然而,这一领域仍有许多未知之处。本研究利用生物信息学工具构建了线粒体代谢相关基因(MMRG)的预后模型,以评估PAAD患者的生存、免疫状态、突变谱和药物敏感性。采用单变量Cox回归和LASSO回归筛选差异表达基因(DEG),并使用多元Cox回归建立风险模型。 Kaplan-Meier 估计器用于识别与总生存 (OS) 相关的 MMRG 特征。 ROC 曲线用于评估模型的性能。应用 Maftools、immunodeconv 和 CIBERSORT R 软件包来分析基因突变谱和免疫状态。使用 oncoPredict R 软件包评估对药物的相应敏感性。开发了具有五个 MMRG 的预后模型,该模型将患者定义为高风险,显示较低的生存率。被归类为高风险的个体之间具有良好的一致性,显示出遗传改变率升高,特别是在 TP53 和 KRAS 基因中。此外,这些患者表现出免疫抑制水平增加,其特征是巨噬细胞、中性粒细胞、Th2 细胞和调节性 T 细胞的存在增加。此外,高风险患者对 Sabutoclax 和 Venetoclax 表现出更高的敏感性。通过利用与线粒体代谢相关的基因特征,建立了一个预后模型,该模型可能是预测 PAAD 患者结果的高效方法。© 2024。作者(s)。
Pancreatic ductal adenocarcinoma (PAAD) is recognized as an exceptionally aggressive cancer that both highly lethal and unfavorable prognosis. The mitochondrial metabolism pathway is intimately involved in oncogenesis and tumor progression, however, much remains unknown in this area. In this study, the bioinformatic tools have been used to construct a prognostic model with mitochondrial metabolism-related genes (MMRGs) to evaluate the survival, immune status, mutation profile, and drug sensitivity of PAAD patients.Univariate Cox regression and LASSO regression were used to screen the differentially expressed genes (DEGs), and multivariate Cox regression was used to develop the risk model. Kaplan-Meier estimator was employed to identify MMRGs signatures associated with overall survival (OS). ROC curves were utilized to evaluate the model's performance. Maftools, immunedeconv and CIBERSORT R packages were applied to analyze the gene mutation profiles and immune status. The corresponding sensitivity to pharmaceutical agents was assessed using oncoPredict R packages.A prognostic model with five MMRGs was developed, which defined the patients as high-risk showed lower survival rates. There was good consistency among individuals categorized as high-risk, showing elevated rates of genetic alterations, particularly in the TP53 and KRAS genes. Furthermore, these patients exhibited increased levels of immunosuppression, characterized by an increased presence of macrophages, neutrophils, Th2 cells, and regulatory T cells. Additionally, high-risk patients showed increased sensitivity to Sabutoclax and Venetoclax.By utilizing a gene signature associated with mitochondrial metabolism, a prognostic model has been established which could be a highly efficient method for predicting the outcomes of PAAD patients.© 2024. The Author(s).