RESUMO
The molecular mechanisms underlying chemoresistance in some newly diagnosed multiple myeloma (MM) patients receiving standard therapies (lenalidomide, bortezomib, and dexamethasone) are poorly understood. Identifying clinically relevant gene networks associated with death due to MM may uncover novel mechanisms, drug targets, and prognostic biomarkers to improve the treatment of the disease. This study used data from the MMRF CoMMpass RNA-seq dataset (N = 270) for weighted gene co-expression network analysis (WGCNA), which identified 21 modules of co-expressed genes. Genes differentially expressed in patients with poor outcomes were assessed using two independent sample t-tests (dead and alive MM patients). The clinical performance of biomarker candidates was evaluated using overall survival via a log-rank Kaplan-Meier and ROC test. Four distinct modules (M10, M13, M15, and M20) were significantly correlated with MM vital status and differentially expressed between the dead (poor outcomes) and the alive MM patients within two years. The biological functions of modules positively correlated with death (M10, M13, and M20) were G-protein coupled receptor protein, cell-cell adhesion, cell cycle regulation genes, and cellular membrane fusion genes. In contrast, a negatively correlated module to MM mortality (M15) was the regulation of B-cell activation and lymphocyte differentiation. MM biomarkers CTAG2, MAGEA6, CCND2, NEK2, and E2F2 were co-expressed in positively correlated modules to MM vital status, which was associated with MM's lower overall survival.
RESUMO
INTRODUCTION: A significant chunk of global life - the economy, sports, aviation, academic, and entertainment activities - has significantly been affected by the ravaging outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) with devastating consequences on morbidity and mortality in many countries of the world. METHODS: This review utilized search engines such as google scholar, PubMed, ResearchGate, and web of science to retrieve articles and information using keywords like "Coronavirus", "SARS-CoV-2", "COVID-19", "Origin of coronavirus and SARS-CoV-2", "microbiology of coronavirus", "microbiology of SARS-CoV-2", COVID-19", "Coronavirus reservoir sites", "Anatomic sanctuary sites and SARS-CoV-2", biological barriers and coronavirus", biological barrier and SARS-CoV-2". RESULTS: While this pandemic has caught the global scientific community at its lowest level of preparedness, it has inadvertently created a unified and wholesome approach towards developing potential vaccine (s) candidates by escalating clinical trial protocols in many countries of Europe, China and the United States. Interestingly, viral pathobiology continues to be an evolving aspect that potentially shows that the management of the current outbreak may largely depend on the discovery of a vaccine as the administration of known antiviral drugs are proving to offer some respite. Unfortunately, discontinuation and longtime administration of these drugs have been implicated in endocrine, reproductive and neurological disorders owing to the development of pathological lesions at anatomical sanctuary sites such as the brain and testis, as well as the presence of complex biological barriers that permit the entry of viruses but selective to the entrance of chemical substances and drugs. CONCLUSION: This review focuses on the microbiologic perspectives and importance of anatomical sanctuary sites in the possible viral rebound or reinfection into the system and their implications in viral re-entry and development of reproductive and neurological disorders in COVID-19 patients.
