■肺腺癌(LUAD)患者感染COVID-19的风险很高,从全球差异表达格局的角度,对LUAD患者对COVID-19高度易感性的分子机制的研究还很少。
■从全球差异表达格局的角度填补了LUAD患者对COVID-19高易感性的分子机制的研究空白。
■这里,我们确定了基因,特别是差异表达基因(DEGs),与LUAD患者对COVID-19的易感性相关。这些是通过计算49个SARS-CoV-2感染的LUAD样品和24个未受影响的LUAD样品的标准平均偏差(SMD)值获得的,以及来自40个合并RNA-seq和微阵列数据集的3931个LUAD样品和3027个非癌肺样品。通过加权基因共表达网络分析进一步筛选出与COVID-19显著相关的集线器易感基因。然后,通过检查其在多个数据集中的临床意义来进一步分析hub基因,免疫细胞浸润水平的相关性分析,以及它们与A549细胞系相互作用组的相互作用。
■共鉴定出257个易感基因,这些基因与RNA剪接有关,线粒体功能,和蛋白酶体。十个基因,MEA1,MRPL24,PPIH,EBNA1BP2,MRTO4,RABEPK,TRMT112、PFDN2、PFDN6和NDUFS3被证实是LUAD患者COVID-19的中心易感基因,hub易感基因与多种免疫细胞浸润显著相关。
■总而言之,本研究中发现的LUAD患者COVID-19的易感基因可能会增加我们对LUAD患者COVID-19高风险的理解.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.