RESUMEN
BACKGROUND: Multiple myeloma (MM) is a hematological malignancy. Coronavirus disease 2019 (COVID-19) infection correlates with MM features. This study aimed to identify MM prognostic biomarkers with potential association with COVID-19. METHODS: Differentially expressed genes (DEGs) in five MM data sets (GSE47552, GSE16558, GSE13591, GSE6477, and GSE39754) with the same expression trends were screened out. Functional enrichment analysis and the protein-protein interaction network were performed for all DEGs. Prognosis-associated DEGs were screened using the stepwise Cox regression analysis in the cancer genome atlas (TCGA) MMRF-CoMMpass cohort and the GSE24080 data set. Prognosis-associated DEGs associated with COVID-19 infection in the GSE164805 data set were also identified. RESULTS: A total of 98 DEGs with the same expression trends in five data sets were identified, and 83 DEGs were included in the protein-protein interaction network. Cox regression analysis identified 16 DEGs were associated with MM prognosis in the TCGA cohort, and only the cytochrome c oxidase subunit 6C (COX6C) gene (HR = 1.717, 95% CI 1.231-2.428, p = .002) and the nucleotide-binding oligomerization domain containing 2 (NOD2) gene (HR = 0.882, 95% CI 0.798-0.975, p = .014) were independent factors related to MM prognosis in the GSE24080 data set. Both of them were downregulated in patients with mild COVID-19 infection compared with controls but were upregulated in patients with severe COVID-19 compared with patients with mild illness. CONCLUSIONS: The NOD2 and COX6C genes might be used as prognostic biomarkers in MM. The two genes might be associated with the development of COVID-19 infection.
Asunto(s)
COVID-19/genética , Biología Computacional/métodos , Perfilación de la Expresión Génica , Mieloma Múltiple/genética , SARS-CoV-2 , COVID-19/mortalidad , Conjuntos de Datos como Asunto , Complejo IV de Transporte de Electrones/genética , Regulación Neoplásica de la Expresión Génica , Regulación Viral de la Expresión Génica , Ontología de Genes , Humanos , Estimación de Kaplan-Meier , Análisis por Micromatrices , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Proteína Adaptadora de Señalización NOD2/genética , Pronóstico , Modelos de Riesgos Proporcionales , Mapas de Interacción de Proteínas/genéticaRESUMEN
Background: Angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) allow entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells and play essential roles in cancer therapy. However, the functions of ACE2 and TMPRSS2 in kidney cancer remain unclear, especially as kidneys are targets for SARS-CoV-2 infection. Methods: UCSC Xena project, the Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) databases (GSE30589 and GSE59185) were searched for gene expression in human tissues, gene expression data, and clinical information. Several bioinformatics methods were utilized to analyze the correlation between ACE2 and TMPRSS2 with respect to the prognosis of kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP). Results: ACE2 expression was significantly upregulated in tumor tissue, while its downregulation was associated with low survival in KIRC and KIRP patients. TMPRSS2 was downregulated in KIRC and KIRP, and its expression was not correlated with patient survival. According to clinical risk factor-based prediction models, ACE2 exhibits predictive accuracy for kidney cancer prognosis and is correlated with metabolism and immune infiltration. In an animal model, ACE2 expression was remarkably downregulated in SARS-CoV-2-infected cells compared to in the control. Conclusion: ACE2 expression is highly correlated with various metabolic pathways and is involved in immune infiltration.it plays a crucial role than TMPRSS2 in diagnosing and prognosis of kidney cancer patients. The overlap in ACE2 expression between kidney cancer and SARS-CoV-2 infection suggests that patients with KIRC or KIRP are at high risk of developing serious symptoms.
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Enzima Convertidora de Angiotensina 2/biosíntesis , COVID-19/complicaciones , Carcinoma de Células Renales/complicaciones , Neoplasias Renales/complicaciones , Receptores Virales/biosíntesis , SARS-CoV-2 , Adulto , Anciano , Enzima Convertidora de Angiotensina 2/genética , Enzima Convertidora de Angiotensina 2/fisiología , Animales , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/mortalidad , Chlorocebus aethiops , Regulación hacia Abajo , Resistencia a Antineoplásicos , Femenino , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/inmunología , Neoplasias Renales/metabolismo , Neoplasias Renales/mortalidad , Linfocitos Infiltrantes de Tumor/inmunología , Masculino , Persona de Mediana Edad , Modelos Animales , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Especificidad de Órganos , Pronóstico , Modelos de Riesgos Proporcionales , Receptores Virales/genética , Sistema Renina-Angiotensina/fisiología , Serina Endopeptidasas/biosíntesis , Serina Endopeptidasas/genética , Serina Endopeptidasas/fisiología , Análisis de Matrices Tisulares , Células VeroRESUMEN
PURPOSE: Owing to its worldwide spread, the coronavirus disease (COVID-19) epidemic was declared a pandemic by the World Health Organization on March 11, 2020. Angiotensin-converting enzyme 2 (ACE2) is the outer surface protein of the cell membrane that is abundantly distributed in the heart, lungs, and kidneys and plays an important role in molecular docking of the severe acute respiratory syndrome coronavirus 2. In this study, we aimed to analyze the difference in the survival rate according to ACE2 expressions in pan-cancer. MATERIALS AND METHODS: We downloaded clinical and genomic data from The Cancer Genome Atlas. We used Kaplan-Meier with a log-rank test, and the Cox proportional hazards regression to analyze prognostic significance. RESULTS: In the Kaplan-Meier curve, clear cell renal cell carcinoma (ccRCC), uveal melanoma, and prostate adenocarcinoma showed statistical significance. In the Cox regression, thyroid carcinoma and glioblastoma multiforme and ccRCC showed significant results. Only ccRCC had statistical significance, and high ACE2 expression is related to good prognosis. It is known that the ACE inhibitor, a primary antihypertensive agent, increases ACE2 expression. CONCLUSION: Based on these results, we believe that the ACE inhibitor will be important to increase the lifespan of ccRCC patients. This study is the first research to offer a recommendation on the use of anti-hypertensive drugs to ccRCC patients.
Asunto(s)
Enzima Convertidora de Angiotensina 2/biosíntesis , Antihipertensivos/administración & dosificación , Tratamiento Farmacológico de COVID-19 , COVID-19 , Carcinoma de Células Renales , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias Renales , Proteínas de Neoplasias/biosíntesis , COVID-19/metabolismo , COVID-19/mortalidad , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/metabolismo , Neoplasias Renales/mortalidad , Masculino , Tasa de SupervivenciaRESUMEN
The recent outbreak of infections and the pandemic caused by SARS-CoV-2 represent one of the most severe threats to human health in more than a century. Emerging data from the United States and elsewhere suggest that the disease is more severe in men. Knowledge gained, and lessons learned, from studies of the biological interactions and molecular links that may explain the reasons for the greater severity of disease in men, and specifically in the age group at risk for prostate cancer, will lead to better management of COVID-19 in prostate cancer patients. Such information will be indispensable in the current and post-pandemic scenarios.