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

https://doi.org/10.1016/j.csbj.2021.11.026Get rights and content
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Abstract

Introduction

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.

Objectives

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.

Methods

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.

Results

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.

Conclusion

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.

Keywords

LUAD
COVID-19
DEG
Susceptibility
Immune infiltration
WGCNA

Abbreviations

LUAD
lung adenocarcinoma
DEG
differentially expressed genes
SMD
standard mean difference
COVID-19
coronavirus disease 2019
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
WGCNA
weighted gene co-expression network analysis
FPKM
fragments per kilobase per million
TPM
transcripts per million reads
GTEx
Genotype-tissue Expression
FC
fold change
CI
confidence interval
PPI
protein-to-protein interaction
SROC
summarized receiver’s operating characteristics
IHC
immunohistochemistry
HPA
human protein atlas
TF
transcription factor

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