A Novel Mitochondrial-Related Nuclear Gene Signature Predicts Overall Survival of Lung Adenocarcinoma Patients.
A Novel Mitochondrial-Related Nuclear Gene Signature Predicts Overall Survival of Lung Adenocarcinoma Patients.
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一种新的线粒体相关核基因特征可预测肺腺癌患者的总体生存率
DOI：
10.3389/fcell.2021.740487
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发表时间：
2021
影响因子：
5.5
通讯作者：
Ma W
中科院分区：
文献类型：
--
作者：
Zhang X;Dong W;Zhang J;Liu W;Yin J;Shi D;Ma W
背景资料：肺癌是世界范围内癌症相关死亡的主要原因，其中肺腺癌（LUAD）是主要的组织学亚型之一。线粒体对于维持生理功能至关重要，并且已发现其功能障碍与肿瘤发生和疾病进展相关。尽管如此，一些肿瘤相关基因已被发现与多种肿瘤的临床结果单独相关。核线粒体基因（NMGs）与LUAD预后的整合关系尚不清楚。方法：从公共数据库下载LUAD的NMG列表、基因表达数据和相关临床信息。采用生物信息学方法，获得18个与预后相关的NMG，构建风险特征。结果如下：LASSO回归分析鉴定出18个NMG（NDUF S2、ATP 8A2、SCO1、COX 14、COA 6、RRM2B、TFAM、DARS2、加尔斯、YARS 2、EFG 1、GFM1、MRPL 3、MRPL 44、ISCU、CABC 1、HSPD 1和ETHE 1）。这18个基因的mRNA表达量与其相对线性拷贝数变化（CNA）呈正相关。同时，建立的风险签名可以有效区分高风险和低风险患者，其预测能力在三个独立的基因表达综合（GEO）队列中得到验证。值得注意的是，在具有高风险NMG特征但伴有更发炎的免疫肿瘤微环境的患者中，可采取行动的EGFR改变的患病率显著较低。此外，多因素考克斯回归分析显示，当考虑风险评分、肿瘤分期和淋巴结分期时，模型稳定，1年、3年和5年AUC分别为0.74、0.75和0.70。结论：总之，这项研究建立了一个基于NMG的签名，这是LUAD患者的预后生物标志物，并有可能在未来的临床环境中广泛应用。
Background: Lung cancer is the leading cause of cancer-related death worldwide, of which lung adenocarcinoma (LUAD) is one of the main histological subtypes. Mitochondria are vital for maintaining the physiological function, and their dysfunction has been found to be correlated with tumorigenesis and disease progression. Although, some mitochondrial-related genes have been found to correlate with the clinical outcomes of multiple tumors solely. The integrated relationship between nuclear mitochondrial genes (NMGs) and the prognosis of LUAD remains unclear. Methods: The list of NMGs, gene expression data, and related clinical information of LUAD were downloaded from public databases. Bioinformatics methods were used and obtained 18 prognostic related NMGs to construct a risk signature. Results: There were 18 NMGs (NDUFS2, ATP8A2, SCO1, COX14, COA6, RRM2B, TFAM, DARS2, GARS, YARS2, EFG1, GFM1, MRPL3, MRPL44, ISCU, CABC1, HSPD1, and ETHE1) identified by LASSO regression analysis. The mRNA expression of these 18 genes was positively correlated with their relative linear copy number alteration (CNA). Meanwhile, the established risk signature could effectively distinguish high- and low-risk patients, and its predictive capacity was validated in three independent gene expression omnibus (GEO) cohorts. Notably, a significantly lower prevalence of actionable EGFR alterations was presented in patients with high-risk NMGs signature but accompanied with a more inflame immune tumor microenvironment. Additionally, multicomponent Cox regression analysis showed that the model was stable when risk score, tumor stage, and lymph node stage were considered, and the 1-, 3-, and 5-year AUC were 0.74, 0.75, and 0.70, respectively. Conclusion: Together, this study established a signature based on NMGs that is a prognostic biomarker for LUAD patients and has the potential to be widely applied in future clinical settings.
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影响因子：
16.6
作者：
Hopkins JF;Sabelnykova VY;Weischenfeldt J;Simon R;Aguiar JA;Alkallas R;Heisler LE;Zhang J;Watson JD;Chua MLK;Fraser M;Favero F;Lawerenz C;Plass C;Sauter G;McPherson JD;van der Kwast T;Korbel J;Schlomm T;Bristow RG;Boutros PC
通讯作者：
Boutros PC
影响因子：
12.7
作者：
Hartmann, Christian;Meyer, Jochen;von Deimling, Andreas
通讯作者：
von Deimling, Andreas
影响因子：
5.2
作者：
Bonora M;Missiroli S;Perrone M;Fiorica F;Pinton P;Giorgi C
通讯作者：
Giorgi C
影响因子：
30.8
作者：
BOURGERON, T;RUSTIN, P;ROTIG, A
通讯作者：
ROTIG, A
影响因子：
20.1
作者：
Dunham-Snary, Kimberly J.;Wu, Danchen;Archer, Stephen L.
通讯作者：
Archer, Stephen L.