Identification of the susceptibility genes for COVID-19 in lung adenocarcinoma with global data and biological computation methods.

Identification of the susceptibility genes for COVID-19 in lung adenocarcinoma with global data and biological computation methods.
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DOI:
10.1016/j.csbj.2021.11.026
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发表时间:
2021
影响因子:
6
通讯作者:
Chen G
Chen G
中科院分区:
生物学2区
文献类型:
--
作者:
Gao L;Li GS;Li JD;He J;Zhang Y;Zhou HF;Kong JL;Chen G

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肺腺癌患者感染新冠肺炎的风险很高,而从全球差异表达格局的角度研究肺腺癌患者对新冠肺炎的高易感性的分子机制的研究还很少。以填补从全球差异表达格局角度对LUAD患者对新冠肺炎高度易感的分子机制的研究空白。在此,我们发现了与LUAD患者对新冠肺炎易感性相关的基因,特别是差异表达基因(DEG)。这些是通过计算49个感染SARS-CoV-2的LUAD样本和24个未受影响的LUAD样本的标准平均偏差(SMD)值,以及来自40个汇集的RNA-SEQ和微阵列数据集的3931个LUAD样本和3027个非癌症肺样本的标准平均偏差(SMD)值获得的。通过加权基因共表达网络分析进一步筛选出与新冠肺炎显著相关的HUB易感基因。然后,通过检查它们在多个数据集中的临床意义、免疫细胞渗透水平的相关性分析以及它们与A549细胞系相互作用组集的相互作用,进一步分析了HUB基因。共鉴定出257个易感基因,这些基因与RNA剪接、线粒体功能和蛋白酶体相关。MEA1、MRPL24、PIH、EBNA1BP2、MRTO4、RABEPK、TRMT112、PFDN2、PFDN6和NDUFS3等10个基因是LUAD患者新冠肺炎的中枢易感基因,且这些易感基因与多个免疫细胞的浸润密切相关。综上所述,本研究发现的LUAD患者发生新冠肺炎的易感基因可能会增加我们对LUAD患者发生新冠肺炎高危的认识。
The risk of infection with COVID-19 is high in lung adenocarcinoma (LUAD) patients, and there is a dearth of studies on the molecular mechanism underlying the high susceptibility of LUAD patients to COVID-19 from the perspective of the global differential expression landscape. To fill the research void on the molecular mechanism underlying the high susceptibility of LUAD patients to COVID-19 from the perspective of the global differential expression landscape. Herein, we identified genes, specifically the differentially expressed genes (DEGs), correlated with the susceptibility of LUAD patients to COVID-19. These were obtained by calculating standard mean deviation (SMD) values for 49 SARS-CoV-2-infected LUAD samples and 24 non-affected LUAD samples, as well as 3931 LUAD samples and 3027 non-cancer lung samples from 40 pooled RNA-seq and microarray datasets. Hub susceptibility genes significantly related to COVID-19 were further selected by weighted gene co-expression network analysis. Then, the hub genes were further analyzed via an examination of their clinical significance in multiple datasets, a correlation analysis of the immune cell infiltration level, and their interactions with the interactome sets of the A549 cell line. A total of 257 susceptibility genes were identified, and these genes were associated with RNA splicing, mitochondrial functions, and proteasomes. Ten genes, MEA1, MRPL24, PPIH, EBNA1BP2, MRTO4, RABEPK, TRMT112, PFDN2, PFDN6, and NDUFS3, were confirmed to be the hub susceptibility genes for COVID-19 in LUAD patients, and the hub susceptibility genes were significantly correlated with the infiltration of multiple immune cells. In conclusion, the susceptibility genes for COVID-19 in LUAD patients discovered in this study may increase our understanding of the high risk of COVID-19 in LUAD patients.
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