Association of ACE and ACE2 genes elevate the risk of lung cancer

Abstract

Abstract Background: ACE and ACE2 are biologically potential biomarkers responsible for the production and progression of lung cancer. Multiple factors and bioprocesses are associated with in tumorigenesis and metastasis of lung cancer, including cellular senescence and immune evasion. We aimed to analyzed the expression and association of ACE and ACE2 genes in lung cancer & Covid-19. We also aimed to identify prognostic and immune-meditating effects of ACE and ACE2 in lung cancer. Subjects and methods: Web-based bioinformatics tools were used to assess the association of ACE and ACE2 with lung cancer risks. The prognostic significance of mRNA expression of ACE and ACE2 in lung cancer were evaluated using the Kaplan–Meier plotter. Correlation analyses were performed to reveal the association among key factor, immune infiltration, T cell biomarkers and immune checkpoints. Univariate and multivariate Cox proportional hazards regression analysis were performed to determine whether ACE and ACE2 are an independent risk factor for overall survival (OS) and fast progression (FP) of lung cancer patients. Additionally, STRING database was used to analyze protein-protein interactions. Result: Our data confirmed that ACE is significantly expressed and associated with higher lung cancer risks where ACE2 role in developing lung cancer is controversial but in Covid-19. Moreover, high expression of ACE and ACE2 might predict poor OS and FP in lung cancer patients. Besides, disease stage and expression level of ACE and ACE2 were correlated with fast progression and overall survival in lung cancer. Both ACE and ACE2 were found highly co-expressed with different immune checkpoints. Analysis of protein-protein interaction based on STRING database gained top 10 genes which could interact with ACE (including, AGT, KNG1, REN, RHOA, RHOC, ATTR1, AGTR2, BDKRB2, MME and NR3C2) and ACE2 (including, SLC6A19, AGT, DPP4, REN, MME, PRCP, MEPIA, SLC1A7, TMPRSS2 and CLEC4M) Conclusion: Our results indicate that, aberrant expression of ACE in lung cancer is greater than ACE2 and might be involved in the pathogenesis of lung cancer risk whereas ACE2 in Covid-19.