Renal Carcinoma Is Associated With Increased Risk of Coronavirus Infections

  1. Satyendra C. Tripathi
  2. Vishwajit Deshmukh
  3. Chad J. Creighton
  4. Ashlesh Patil

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Abstract

Background: The current COVID-19 pandemic has affected most severely people with old age, or with comorbidities like hypertension, diabetes mellitus, and cancer. Cancer patients are twice more likely to contract the disease because of the malignancy or treatment-related immunosuppression; hence identification of the vulnerable population among these patients is essential.

Method: We took a bioinformatics approach to analyze the gene and protein expression data of these coronavirus receptors (DPP4, ANPEP, ENPEP, TMPRSS2) in human normal and cancer tissues of multiple organs including the brain, liver, kidney, heart, lung, skin, GI tract, pancreas, endocrine tissues, and the reproductive organs. RNA-Seq data from The Cancer Genome Atlas (TCGA) and GTeX databases were used for extensive profiling analysis of these receptors across 9,736 tumors and 8,587 normal tissues comparing coronavirus receptors. Protein expression from immunohistochemistry data was assessed from The Human Protein Atlas database including 144 samples, corresponding to 48 different normal human tissue types, and 432 tumor samples from 216 different cancer patients. The correlations between immune cell infiltration, chemokine, and cytokines were investigated via Tumor Immune Estimation Resource (TIMER) and TCGA.

Result: We found that among all, renal tumor and normal tissues exhibited increased levels of ACE2, DPP4, ANPEP, and ENPEP. Our results revealed that TMPRSS2 may not be the co-receptor for coronavirus infection in renal carcinoma patients. The other receptors DPP4, ANPEP, and ENPEP may act as the compensatory receptor proteins to help ACE2. The receptors' expression levels were variable in different tumor stage, molecular, and immune subtypes of renal carcinoma. Intriguingly, in clear cell renal cell carcinomas, coronavirus receptors were associated with high immune infiltration, markers of immunosuppression, and T cell exhaustion.

Conclusion: Our study indicates that CoV receptors may play an important role in modulating the immune infiltrate and hence cellular immunity in renal carcinoma. As our current knowledge of pathogenic mechanisms will improve, it may help us in designing focused therapeutic approaches.

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  1. Version published to 10.3389/fmolb.2020.579422
  2. ScreenIT

    SciScore for 10.1101/2020.07.02.184663: (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
    For analyses of interactions among CoV receptors, the STRING database, which enables analysis for the structural and functional component of proteins (Szklarczyk et al., 2017)was used.
    STRING
    suggested: (STRING, RRID:SCR_005223)
    For preparing the bar graph, the data was analyzed using GraphPad™ software (version 6.01, GraphPad Software, Inc., USA) and presented as mean ± SD. p-values < 0.05 were considered statistically significant.
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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: We detected the following sentences addressing limitations in the study:
    Our study has some limitations as our findings are based on correlation and associations drawn on analysis of data extracted from several public databases. Further experiments are warranted to confirm the role of CoV receptors in immune modulation of renal carcinoma. In conclusion, our bioinformatics analysis revealed that renal carcinoma patients might be more susceptible to CoV infection. We found evidence that TMPRSS2 may not be the auxiliary protein for coronavirus infection in renal carcinoma. ACE2 and DPP4 increased expression in renal carcinoma tissues as compared to normal kidney. This association suggests that these patients are at increased risk of case related fatalities than healthy subjects. ACE2, DPP4, ANPEP, and ENPEP each associated with a high level of immune infiltration, inflammatory chemokines, cytokines and markers of an immunosuppressive microenvironment and T cell exhaustion in KIRC tumors. Our study indicates that CoV receptors may play an important role in modulating the immune infiltrate and hence cellular immunity in renal carcinoma.

    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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2020.07.02.184663v1 on bioRxiv