An investigation into the molecular basis of cancer comorbidities in coronavirus infection.

Comorbidities in COVID-19 patients often worsen clinical conditions and may represent death predictors. Here, the expression of 5 genes, known to encode coronavirus receptors/interactors (ACE2, TMPRSS2, CLEC4M, DPP4 and TMPRSS11D), was investigated in normal and cancer tissues, and their molecular relationships with clinical comorbidities were investigated. Using expression data from GENT2 databases, we evaluated gene expression in all anatomical districts from 32 normal tissues in 3,902 individuals. Functional relationships with body districts were analyzed by Chilibot. We performed DisGeNet, GeneMania and DAVID analyses to identify human diseases associated with these genes. Transcriptomic-expression levels were then analyzed in 31 cancer-types and healthy controls from about 43,000 individuals, using GEPIA2 and GENT2 databases. By performing ROC analysis, Area Under Curve (AUC) was used to discriminate healthy from cancer patients. Coronavirus receptors were found to be expressed in several body districts. Moreover, the 5 genes were found to associate with acute respiratory syndrome, diabetes, cardiovascular diseases and cancer, i.e., the most frequent COVID-19 comorbidities. Their expression levels were found to be significantly altered in cancer types including colon, kidney, liver, testis, thyroid and skin cancers, (p 0.80 suggests TMPRSS2, CLEC4M and DPP4 as relevant markers of kidney, liver, and thyroid cancer, respectively. The five coronavirus receptors are related to all main COVID-19 comorbidities and three show significantly different expression in cancer vs control tissues. Further investigation into their role may help in monitoring other comorbidities as well as for follow-up of patients who have recovered from SARS-CoV-2 infection.