RESUMO
Lung cancer patients with COVID-19 present an increased risk of developing severe disease and, consequently, have poor outcomes. Determining SARS-CoV-2-host interactome in lung cancer cells and tissues, infected or uninfected with SARS-CoV-2, may reveal molecular mechanisms associated with COVID-19 development and severity in lung cancer patients. Here, we integrated transcriptome data of lung tumors from patients with small- or non-small cell lung cancer (SCLC and NSCLC) and normal lung and lung cancer cells infected with SARS-CoV-2. We aimed to characterize molecular mechanisms potentially associated with COVID-19 development and severity in lung cancer patients and to predict the SARS-CoV-2-host cell interactome. We found that the gene expression profiles of lung cell lines infected with SARS-CoV-2 resemble more primary lung tumors than non-malignant lung tissues. In addition, the transcriptomic-based interactome analysis of SCLC and NSCLC revealed increased expression of cancer genes BRCA1 and CENPF, whose proteins are known or predicted to interact with the SARS-CoV-2 spike glycoprotein and helicase, respectively. We also found that TRIB3, a gene coding a putative host-SARS-CoV-2 interacting protein associated with COVID-19 infection, is co-expressed with the up-regulated genes MTHFD2, ADM2, and GPT2 in all tested conditions. Our analysis identified biological processes such as amino acid metabolism and angiogenesis and 22 host mediators of SARS-CoV-2 infection and replication that may contribute to the development and severity of COVID-19 in lung cancers.
Assuntos
COVID-19 , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Transcriptoma , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , COVID-19/genética , COVID-19/patologia , Pulmão/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , SARS-CoV-2Assuntos
Doença Granulomatosa Crônica/complicações , Doença Granulomatosa Crônica/genética , NADPH Oxidases/genética , Tuberculose Pulmonar/imunologia , Adulto , Antituberculosos/uso terapêutico , Biópsia , Brasil , Feminino , Humanos , Mutação , Fagócitos/enzimologia , Fagócitos/patologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/patologia , Adulto JovemRESUMO
X-linked ectodermal dysplasia with immunodeficiency (XL-EDA-ID) is caused by mutations in the nuclear factor-kappa B essential modulator (NEMO) gene. Here, we report the clinical and genetic features of a XL-EDA-ID patient who developed bacillus Calmette-Guerin infection. Patient lymphocytes failed to degrade IB-, and sequencing of NEMO identified the novel mutation c.1238A>C/p.H413P. Furthermore, patient monocyte-derived macrophages ingested Mycobacterium tuberculosis normally, but failed to control the intracellular proliferation of bacilli, a defect which was improved in the presence of interferon-gamma (IFN-). This work expands the genetic spectrum of XL-EDA-ID and demonstrates improvement in macrophage function in a NEMO-deficient patient by IFN-