对于胶质瘤患者中线粒体相关基因的新预测特征和个体化治疗策略。
Novel prognostic features and personalized treatment strategies for mitochondria-related genes in glioma patients.
发表日期:2023
作者:
Ji Wu, Jiabin Zhou, Yibo Chai, Chengjian Qin, Yuankun Cai, Dongyuan Xu, Yu Lei, Zhimin Mei, Muhua Li, Lei Shen, Guoxing Fang, Zhaojian Yang, Songshan Cai, Nanxiang Xiong
来源:
Frontiers in Endocrinology
摘要:
胶质瘤是最常见的颅内神经系统肿瘤,高度恶性和侵袭性,线粒体是肿瘤细胞代谢重编程的重要标志,目前的组织病理学不能准确预测预后。因此,需要鉴定一个带有免疫相关特征的线粒体基因,可用于预测胶质瘤患者的预后。胶质瘤数据从TCGA数据库下载,线粒体相关基因从MITOCARTA 3.0数据集获得。使用CGGA,Kamoun和Gravendeel数据库作为外部数据集。应用LASSO(最小绝对值估计和选择算子)回归来确定预后特征,利用ROC曲线下的面积和评分表来评估模型的稳健性。采用单个样本基因组富集分析(ssGSEA)来探索模型基因与免疫浸润之间的关系,并使用药物敏感性来识别定位药物。然后进行细胞研究以证明药物对肿瘤的杀伤作用。COX组装线粒体蛋白同源物(CMC1),细胞色素C氧化酶蛋白20同源物(COX20)和细胞色素b-c1复合物亚基7(UQCRB)在胶质瘤中被鉴定为预后关键基因,其中UQCRB和CMC1随着风险评分的降低逐渐增加,而COX20则逐渐降低。TCGA训练集模型的ROC曲线分析显示,在1年、2年和3年生存方面,都可以获得>0.8的AUC(曲线下面积)值,该模型与CD8+T细胞和免疫检查点有关。最后,使用cellMiner数据库和分子对接验证了UQCRB通过位于78位的赖氨酸和82位的苏氨酸与Amonafide共价结合,而细胞实验表明Amonafide抑制胶质瘤的迁移和侵袭。我们的三个与线粒体基因组成相关的特征可以准确预测胶质瘤患者的预后,并且我们还提供了可能与线粒体相关的靶向胶质瘤化疗药物。版权所有©2023年Wu,Zhou,Chai,Qin,Cai,Xu,Lei,Mei,Li,Shen,Fang,Yang,Cai和Xiong。
Gliomas are the most common intracranial nervous system tumours that are highly malignant and aggressive, and mitochondria are an important marker of metabolic reprogramming of tumour cells, the prognosis of which cannot be accurately predicted by current histopathology. Therefore, Identify a mitochondrial gene with immune-related features that could be used to predict the prognosis of glioma patients.Gliomas data were downloaded from the TCGA database and mitochondrial-associated genes were obtained from the MITOCARTA 3.0 dataset. The CGGA, kamoun and gravendeel databases were used as external datasets. LASSO(Least absolute shrinkage and selection operator) regression was applied to identify prognostic features, and area and nomograms under the ROC(Receiver Operating Characteristic) curve were used to assess the robustness of the model. Single sample genomic enrichment analysis (ssGSEA) was employed to explore the relationship between model genes and immune infiltration, and drug sensitivity was used to identify targeting drugs. Cellular studies were then performed to demonstrate drug killing against tumours.COX assembly mitochondrial protein homolog (CMC1), Cytochrome c oxidase protein 20 homolog (COX20) and Cytochrome b-c1 complex subunit 7 (UQCRB) were identified as prognostic key genes in glioma, with UQCRB, CMC1 progressively increasing and COX20 progressively decreasing with decreasing risk scores. ROC curve analysis of the TCGA training set model yielded AUC (Area Under The Curve) values >0.8 for 1-, 2- and 3-year survival, and the model was associated with both CD8+ T cells and immune checkpoints. Finally, using cellMiner database and molecular docking, it was confirmed that UQCRB binds covalently to Amonafide via lysine at position 78 and threonine at position 82, while cellular assays showed that Amonafide inhibits glioma migration and invasion.Our three mitochondrial genomic composition-related features accurately predict Survival in glioma patients, and we also provide glioma chemotherapeutic agents that may be mitochondria-related targets.Copyright © 2023 Wu, Zhou, Chai, Qin, Cai, Xu, Lei, Mei, Li, Shen, Fang, Yang, Cai and Xiong.