TMPRSS2, the SARS-CoV-2 Motivator as a Negative Prognostic Biomarker Decreased in Lung Adenocarcinoma

Yao J and Wang H

Shaoxing Keqiao Women & Children’ Hospital, Zhejiang, China
The Children’s Hospital, Zhejiang University School of Medicine, Keqiao Branch, Zhejiang, China

^*Correspondance to: Hailong Wang 

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Abstract:

Background: Angiotensin-Converting Enzyme (ACE2), Transmembrane Protease Serine 2 (TMPRSS2), Cathepsin L (CTSL) and FURIN are key factors to SARS-CoV-2 infection. We aimed to evaluate the differential expression of ACE2, TMPRSS2, CTSL and FURIN and the association between these four genes and prognosis in NSCLC, and further to explore their susceptibilities to SARS-CoV-2. Methods: A total of 1026 Non-Small Cell Lung Cancer (NSCLC) patients in The Cancer Genome Atlas (TCGA) were enrolled to investigate the association between gene expression of ACE2, TMPRSS2, CTSL as well as FURIN and the overall survival. Then, 920 NSCLC patients from Gene Expression Omnibus (GEO) were analyzed to validate the corresponding genes for prognostic analysis utilizing meta-analysis. Kaplan-Meier curves were also plotted to verify the prognostic value of the respective genes. In addition, we analyzed the correlation between DNA methylation and immune infiltration with gene expression. Ultimately, GSE157057 and GSE163547 datasets were applied to elucidate the changes of TMPRSS2 expression in lung or lung adenocarcinoma cells after SARS-CoV2 infection. Results: TMPRSS2 expression was lower in both LUAD and LUSC tissues compared to normal tissues. DNA methylation level of TMPRSS2 were statistically higher in LUAD and LUSC (LUAD: P=1.62E-12; LUSC: P<1.00E-12). Meta-analysis showed that TMPRSS2 continuous gene expression was significantly correlated with overall survival in LUAD (HR=0.83, 95% CI: 0.59-0.95), which was also verified in Kaplan-Meier plotter database (HR=0.47 (0.36-0.60), log rank P=1.40E-09). The expression of TMPRSS2 in LUAD was positively correlated with the level of immune infiltration of B cell (r=0.242, P=6.66E-08), CD4+ T cells (r=0.244, P=5.51E-08), macrophage (r=0.109, P=1.62E-02) and dendritic cells (r=0.159, P=4.40E-04). Conclusion: TMPRSS2, correlated with immune infiltration, may be a tumor suppressor gene and a prognostic marker in LUAD. Due to the decreased expression of TMPRSS2, LUAD tissues may be more resistant to SARS-CoV-2 infection.

Keywords:

TMPRSS2; Lung adenocarcinoma; Prognosis; SARS-CoV-2

Cite the Article:

Yao J, Wang H. TMPRSS2, the SARS-CoV-2 Motivator as a Negative Prognostic Biomarker Decreased in Lung Adenocarcinoma. Clin Oncol. 2023;8:2018..