Abstract
Coronavirus disease 2019 (COVID-19) is a severe pandemic that has posed an unprecedented challenge to public health worldwide. Hepatocellular carcinoma (HCC) is a common digestive system malignancy, with high aggressiveness and poor prognosis. HCC patients may be vulnerable to COVID-19. Since the anti-inflammatory, immunomodulatory and antiviral effects of vitamin D, we aimed to investigate the possible therapeutic effects and underlying action mechanisms of vitamin D in COVID-19 and HCC in this study. By using a range of bioinformatics and network pharmacology analyses, we identified many COVID-19/HCC target genes and analyzed their prognostic significance in HCC patients. Further, a risk score model with good predictive performance was developed to evaluate the prognosis of HCC patients with COVID-19 based on these target genes. Moreover, we identified seven possible pharmacological targets of vitamin D against COVID-19/HCC, including HMOX1, MB, TLR4, ALB, TTR, ACTA1 and RBP4. And we revealed the biological functions, signaling pathways and TF-miRNA coregulatory network of vitamin D in COVID-19/HCC. The enrichment analysis revealed that vitamin D could help in treating COVID-19/HCC effects through regulation of immune response, epithelial structure maintenance, regulation of chemokine and cytokine production involved in immune response and anti-inflammatory action. Finally, the molecular docking analyses were performed and showed that vitamin D possessed effective binding activity in COVID-19. Overall, we revealed the possible molecular mechanisms and pharmacological targets of vitamin D for treating COVID-19/HCC for the first time. But these findings need to be further validated in actual HCC patients with COVID-19 and need further investigation to confirm.
Keywords: COVID-19; hepatocellular carcinoma; molecular docking; network pharmacology; prognosis; vitamin D.
【저자키워드】 COVID-19, Prognosis, molecular docking, network pharmacology, vitamin D., Hepatocellular carcinoma, 【초록키워드】 public health, Biological functions, Coronavirus disease 2019, immune response, pandemic, Anti-inflammatory, TLR4, bioinformatics, risk, molecular mechanism, chemokine, Antiviral effect, immunomodulatory, signaling pathway, molecular, prognostic, enrichment analysis, epithelial, mechanism, cytokine production, Target genes, HCC, HMOX1, binding activity, malignancy, target gene, Predictive, digestive system, Regulation, poor prognosis, help, therapeutic effect, anti-inflammatory action, pharmacological target, Effect, effective, hepatocellular, HCC patients, aggressiveness, Seven, analyzed, performed, evaluate, involved, analysis, analyses, ACTA1, ALB, HCC patient, RBP4, TTR, with COVID-19, 【제목키워드】 mechanism, identifying, pharmacological target,