Gao Li, Li Guo-Sheng, Li Jian-Di, He Juan, Zhang Yu, Zhou Hua-Fu, Kong Jin-Liang, Chen Gang
Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Rd, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China.
Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324. Jingwu Rd, Jinan, Shandong 250021, PR China.
Comput Struct Biotechnol J. 2021;19:6229-6239. doi: 10.1016/j.csbj.2021.11.026. Epub 2021 Nov 20.
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.
肺腺癌（LUAD）患者感染新型冠状病毒肺炎（COVID-19）的风险很高，而从全球差异表达图谱的角度来看，关于LUAD患者对COVID-19高度易感性的分子机制的研究尚显不足。
从全球差异表达图谱的角度填补关于LUAD患者对COVID-19高度易感性的分子机制的研究空白。
在此，我们鉴定了与LUAD患者对COVID-19易感性相关的基因，特别是差异表达基因（DEG）。这些基因是通过计算49个感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的LUAD样本和24个未受影响的LUAD样本，以及来自40个汇总的RNA测序和微阵列数据集的3931个LUAD样本和3027个非癌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选择与COVID-19显著相关的核心易感性基因。然后，通过检查其在多个数据集中的临床意义、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，对核心基因进行进一步分析。
共鉴定出257个易感性基因，这些基因与RNA剪接、线粒体功能和蛋白酶体有关。MEA1、MRPL24、PPIH、EBNA1BP2、MRTO4、RABEPK、TRMT112、PFDN2、PFDN6和NDUFS3这10个基因被确认为LUAD患者中COVID-19的核心易感性基因，且这些核心易感性基因与多种免疫细胞的浸润显著相关。
总之，本研究中发现的LUAD患者对COVID-19的易感性基因可能会增进我们对LUAD患者中COVID-19高风险的理解。
