Colon Cancer and SARS-CoV-2: Impact of ACE2 Expression in Susceptibility to COVID-19

  1. Mohsen Ahmadi
  2. Negin Saffarzadeh
  3. Mohammad Amin Habibi
  4. Fatemeh Hajiesmaeili
  5. Nima Rezaei

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Abstract

Novel coronavirus disease (COVID-19) pandemic has become a global health emergency. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interacts with angiotensin-converting enzyme 2 (ACE2) to enter the cells and infects diverse human tissues. It has been reported that a few conditions, including cancer, predispose individuals to SARS-CoV-2 infection and severe form of COVID-19. These findings led us to evaluate the susceptibility of colon adenocarcinoma (COAD) patients to SARS-CoV-2 infection by investigation of ACE2 expression in their tumor tissues. The expression analysis revealed that both mRNA and protein levels of ACE2 had increased in colon cancer samples than normal group. Next, the prognosis analysis has indicated that the upregulation of ACE2 was not correlated with patient survival outcomes. Further assessment displayed the hypomethylation of the ACE2 gene promoter in COAD patients. Surprisingly, this methylation status has a strong negative correlation with ACE2 gene expression. The functional enrichment analysis of the genes that had similar expression patterns with ACE2 in colon cancer tissues demonstrated that they mainly enriched in Vitamin digestion and absorption, Sulfur relay system, and Fat digestion and absorption pathways. Finally, we found that ACE2 gene expression had a significant association with the immune cell infiltration levels in COAD patients. In conclusion, it has plausible that COAD patients are more likely to be infected with SARS-CoV-2 and experience severe injuries. Moreover, COVID-19 would bring unfavorable survival outcomes of patients with colon cancer by the way of immune cell infiltration linked process. The present study highlights the importance of preventive actions for COAD patients during the COVID-19 pandemic.

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  1. ScreenIT

    SciScore for 10.1101/2020.06.11.146878: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Expression analysis: The expression levels of the human ACE2 gene in the colon cancer and corresponding control tissues in the TCGA-COAD (Colon Adenocarcinoma) cohort, were assessed by the Gene Expression Profiling Interactive Analysis (GEPIA) 2 (http://gepia2.cancer-pku.cn/#analysis) database (25)
    Gene Expression Profiling Interactive Analysis
    suggested: (Gene Expression Profiling Interactive Analysis, RRID:SCR_018294)
    Confirmatory/Discovery dataset through UALCAN (http://ualcan.path.uab.edu/analysis-prot.html) database (26).
    UALCAN
    suggested: (UALCAN, RRID:SCR_015827)
    KEGG) pathway analysis for these co-expressed genes were obtained from the Enrichr (http://amp.pharm.mssm.edu/Enrichr) database (30). p-value less than 0.05 was set as a cut off criterion.
    KEGG
    suggested: (KEGG, RRID:SCR_012773)
    Immune cell infiltration analysis: We utilized the CIBERSORT algorithm through TIMER 2.0 database (http://timer.cistrome.org/) (31) to evaluate the correlation of the ACE2 expression with immune cells infiltration in COAD, including CD8+ T cell, activated Memory CD4+T cell, resting Memory CD4+T cell, Naive CD4+ T cell, Regulatory T cell (Tregs), Follicular helper T cell, Gamma delta T cell, Memory B cell, Naive B cell, Plasma B cell, Neutrophils, Monocytes, Eosinophils, M0 Macrophages, M1 Macrophages, M2 Macrophages, activated Myeloid Dendritic Cell (DC), resting Myeloid DC,
    TIMER
    suggested: (TIMER, RRID:SCR_018737)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  2. Version published to 10.1101/2020.06.11.146878 on bioRxiv