ACE2 Is a Prognostic Biomarker and Associated with Immune Infiltration in Kidney Renal Clear Cell Carcinoma: Implication for COVID-19

Niu, Xinhao; Zhu, Zhe; Shao, Enming; Bao, Juan Francisco Gibaja

doi:10.1155/2021/8847307

Cited by 13 publications

(13 citation statements)

References 51 publications

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“…However, many KIRC patients still develop drug resistance and progressive diseases, increasing the risk of a poor prognosis [4]. e 5-year overall survival (OS) of stage-IV KIRC patients is less than 10% [5,6]. A recent study revealed that the immune cell response is significantly associated with the prognosis in KIRC [7].…”

Section: Introductionmentioning

confidence: 99%

TLR3 Serves as a Prognostic Biomarker and Associates with Immune Infiltration in the Renal Clear Cell Carcinoma Microenvironment

Liao

et al. 2021

Journal of Oncology

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Background. Clear cell renal cancer (KIRC) is one of the most common cancers globally, with a poor prognosis. TLRs play a vital role in anticancer immunity and the regulation of the biological progress of tumour cells. However, the precise role of TLRs in KIRC is still ambiguous. Methods. Various bioinformatics analysis and clinical validation of tissues were performed to evaluate the prognostic value of TLRs and their correlation with immune infiltration in KIRC. Results. The expression of TLR2/3/7/8 was increased at both mRNA and protein levels in KIRC. TLRs in KIRC were involved in the activation of apoptosis, EMT, RAS/MAPK, and RTK pathways, as well as the inhibition of the cell cycle and the hormone AR pathway. Drug sensitivity analysis revealed that high expression of TLR3 and low expression of TLR7/9/10 were resistant to most of the small molecules or drugs from CTRP. Enrichment analyses showed that TLRs were mainly involved in innate immune response, toll-like receptor signalling pathway, NF-kappa B signalling pathway, and TNF signalling pathway. Furthermore, a high-level TLR3 expression was associated with a favourable prognosis in KIRC. Validation research further confirmed that TLR3 expression was increased in KIRC tissues, and high TLR3 levels were associated with poor overall survival. Moreover, TLR3 in KIRC showed a positive association with an abundance of immune cells, including B-cells, CD4+ T-cells, CD8+ T-cells, macrophage, neutrophils, and dendritic cells, and the expression of the immune biomarker sets. Several TLR3-associated kinase, miRNA, or transcription factor targets were also identified in KIRC. Conclusion. Our results indicate that TLR3 serves as a prognostic biomarker and associated with immune infiltration in KIRC. This work lays a foundation for further studies on the role of TLR3 in the carcinogenesis and progression of KIRC.

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Section: Introductionmentioning

confidence: 99%

TLR3 Serves as a Prognostic Biomarker and Associates with Immune Infiltration in the Renal Clear Cell Carcinoma Microenvironment

Liao

et al. 2021

Journal of Oncology

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“…The ACE inhibitor hypertension drug relieves vasoconstriction by inhibiting ACE expression and increasing ACE2 expression, which restricts the conversion of angiotensin I to angiotensin II [ 45 , 46 , 47 ]. Furthermore, ACE2 expression is inversely related to tumor angiogenesis and progression in many cancers [ 48 , 49 , 50 , 51 , 52 ]. Therefore, future study on KC in vivo should closely monitor RAS regulation and cancer prognosis, which may be caused by KC binding to the ACE2 receptor.…”

Section: Discussionmentioning

confidence: 99%

Mulberry Component Kuwanon C Exerts Potent Therapeutic Efficacy In Vitro against COVID-19 by Blocking the SARS-CoV-2 Spike S1 RBD:ACE2 Receptor Interaction

Kim

Kwon

Kim

et al. 2022

IJMS

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There has been an immense effort by global pharmaceutical companies to develop anti-COVID-19 drugs, including small molecule-based RNA replication inhibitors via drug repositioning and antibody-based spike protein blockers related to cell entry by SARS-CoV-2. However, several limitations to their clinical use have emerged in addition to a lack of progress in the development of small molecule-based cell entry inhibitors from natural products. In this study, we tested the effectiveness of kuwanon C (KC), which has mainly been researched using in silico docking simulation and can serve as an effective building block for developing anti-COVID-19 drugs, in blocking the spike S1 RBD:ACE2 receptor interaction. KC is a natural product derived from Morus alba L., commonly known as mulberry, which has known antiviral efficacy. Molecular interaction studies using competitive ELISA and the BLItz system revealed that KC targets both the spike S1 RBD and the ACE2 receptor, successfully disrupting their interaction, as supported by the in silico docking simulation. Furthermore, we established a mechanism of action by observing how KC prevents the infection of SARS-CoV-2 spike pseudotyped virus in ACE2/TPRSS2-overexpressing HEK293T cells. Finally, we demonstrated that KC inhibits clinical isolates of SARS-CoV-2 in Vero cells. Future combinations of small molecule-based cell entry inhibitors, such as KC, with the currently prescribed RNA replication inhibitors are anticipated to significantly enhance the efficacy of COVID-19 therapies.

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“…We performed gene-disease (GD) analyses to predict signi cant association between DEGs and different diseases. The experiment's outcome showed the top 10 diseases involved in hub DEGs, including Myocardial Infarction,Tumor Angiogenesis,Chronic Kidney Failure,Migraine Disorders,Colorectal Cancer, Colorectal Neoplasms, Squamous cell carcinoma of the head and neck, Cerebrovascular Disorders, Coronary heart disease,Cerebrovascular accident.In our study, we identi ed several diseases associated with both COVID-19 and HF.SARS-COV-2 could lead to a hypercoagulable state and a poor prognosis in patients with acute myocardial infarction (MI), and MI was also an important cause of HF (70).ACE2 was involved in tumor angiogenesis and progression in many malignancies (71).One study showed that SARS-COV-2 uses ACE2 to enter serine protease TMPRSS2 to activate S protein (72). From this point of view,tumor angiogenesis,COVID-19 and HF were related through ACE system.…”

Section: Discussionmentioning

confidence: 99%

Integrated bioinformatics analysis to determine the impact of SARS-CoV-2 infections to Heart Failure patients

Huang

Jiang

et al. 2022

Preprint

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Background:COVID-19, the highly contagious respiratory disease, has become a major threat to humanity, and its extrapulmonary effects were also evident. Heart failure (HF) may be the result of myocardial damage associated with COVID-19. Methods:To understand the relationship between SARS-COV-2 and HF, we used bioinformatics analysis to identify common pathways and molecular biomarkers for HF and COVID-19. In this study, two datasets (GSE152418, GSE57338) from Gene Expression Omnibus (GEO) were used to identify differentially expressed genes (DEGs) of SARS-COV-2 infection in HF patients to find common pathways and drug candidates. Results:A total of 123 common DEGs were identified in the two datasets. Using a variety of bioinformatics tools, we first constructed protein-protein interactions (PPI) and then identified hub genes that could be served as potential biomarkers or novel therapeutic strategies. In addition, some common associations between HF and the progression of COVID-19 infection were found by using functional under ontological terms and pathway analysis. Through the datasets, we also identified transcription factor-gene interactions, protein-drug interactions, and co-regulatory network of DEGs-miRNAs with common DEGs. We built gene-disease association network to represent diseases associated with mutual DEGs.Conclusions:Our study has identified the candidate hub genes and drugs that might become a new therapeutic target for novel coronavirus vaccine development and treatment in COVID-19 and HF.

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ACE2 Is a Prognostic Biomarker and Associated with Immune Infiltration in Kidney Renal Clear Cell Carcinoma: Implication for COVID-19

Cited by 13 publications

References 51 publications

TLR3 Serves as a Prognostic Biomarker and Associates with Immune Infiltration in the Renal Clear Cell Carcinoma Microenvironment

TLR3 Serves as a Prognostic Biomarker and Associates with Immune Infiltration in the Renal Clear Cell Carcinoma Microenvironment

Mulberry Component Kuwanon C Exerts Potent Therapeutic Efficacy In Vitro against COVID-19 by Blocking the SARS-CoV-2 Spike S1 RBD:ACE2 Receptor Interaction

Integrated bioinformatics analysis to determine the impact of SARS-CoV-2 infections to Heart Failure patients

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