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

Abstract

Comorbidities in COVID-19 patients often worsen clinical conditions and may represent death predictors. Here, the expression of five 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 3902 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 approximately 43 000 individuals, using GEPIA2 and GENT2 databases. By performing receiver operating characteristic analysis, the area under the curve (AUC) was used to discriminate healthy from cancer patients. Coronavirus receptors were found to be expressed in several body districts. Moreover, the five 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 < 0.0001); AUC > 0.80 suggests that TMPRSS2, CLEC4M and DPP4 are 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 versus 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. The COVID-19 pandemic is now affecting almost all countries. Patients with severe clinical conditions are often affected by other pathologies, the most frequent being diabetes, coronary heart diseases, cerebrovascular diseases [1] and cancer [2]. SARS-CoV-2 virus directly affects mainly the lung tissues and the higher respiratory tract. Nevertheless, besides the lungs and lung fluids, SARS-CoV-2 has been found in body districts such as feces (approximately 30% of cases) and in the blood (1% of cases) [3]. Furthermore, acute Abbreviations ACE2, angiotensin converting enzyme 2; AUC, area under the curve; CLEC4M, C-type lectin domain family 4 member M; DPP4, dipeptidyl peptidase 4; HCV, hepatitis C virus; ROC, receiver operating characteristic; TMPRSS11D, transmembrane protease serine 11D; TMPRSS2, transmembrane protease serine 2.

Structural Dissection of Viral Spike-Protein Binding of SARS-CoV-2 and SARS-CoV-1 to the Human Angiotensin-Converting Enzyme 2 (ACE2) as Cellular Receptor

“…Different human proteins act as receptors/interactors in coronavirus infection, with consequences in comorbidities [11]. Several studies on SARS-CoV-2 infectivity showed that Angiotensin-Converting Enzyme 2 (ACE2, EC 3.4.17.23), located on the host cell surface, is a protein receptor for this novel coronavirus as well as for SARS-CoV-1, which emerged in 2002 [12][13][14][15][16][17][18][19][20][21].…”

SARS-CoV-2: Emerging Role in the Pathogenesis of Various Thyroid Diseases

“…Similarly, the TMPRSS2 also displays a top-level of its mRNA in the thyroid tissue without reference to gender difference. 24 This once again may facilitate the viral infection to the thyroid that could lead to thyroid dysfunction during and post-COVID-19 cases.

Figure 3 The SARS-CoV-2-induced thyroid dysfunction.

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COVID‑19‑related thyroid conditions (Review)

“…New models of telemedicine allow medical access based on a stratified risk strategy including criteria for deciding thyroid surgery (54). A study on the expression of 5 genes which may interact with the virus such as ACE2, TMPRSS11D, respective TMPRSS2, CLEC4M and DPP4 showed significant alterations in thyroid cancer for the last mentioned three genes (55). However routine genetic testing in non-medullar thyroid cancer is hardly encouraged (56).…”