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3.
Oncology (Williston Park) ; 35(1): 26-28, 2021 Jan 11.
Article in English | MEDLINE | ID: covidwho-1485807

ABSTRACT

Against the difficult and trying backdrop of the pandemic, cancer investigators persisted, and for patients with lung cancer, that persistence paid off in spectacular ways. With several new FDA approved treatments, as well as 2 new targetable mutations in non-small cell lung cancer (NSCLC), 2020 was a banner year in the overall lung cancer space. ONCOLOGY® recently sat down with Jennifer W. Carlisle, MD, of Emory University's Winship Cancer Institute, to discuss the many advances made during the last year for patients with lung cancer along with her hopes for further significant milestones in the year to come.


Subject(s)
COVID-19/epidemiology , Lung Neoplasms/drug therapy , Medical Oncology/organization & administration , Antineoplastic Agents, Immunological/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Humans , Lung Neoplasms/genetics , Precision Medicine , SARS-CoV-2
5.
Cancer Res Treat ; 53(3): 650-656, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1403959

ABSTRACT

PURPOSE: Coronavirus disease 2019 (COVID-19) pandemic has spread worldwide rapidly and patients with cancer have been considered as a vulnerable group for this infection. This study aimed to examine the expressions of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in tumor tissues of six common cancer types. MATERIALS AND METHODS: The expression levels of ACE2 and TMPRSS2 in tumors and control samples were obtained from online databases. Survival prognosis and biological functions of these genes were investigated for each tumor type. RESULTS: There was the overexpression of ACE2 in colon and stomach adenocarcinomas compared to controls, meanwhile colon and prostate adenocarcinomas showed a significantly higher expression of TMPRSS2. Additionally, survival prognosis analysis has demonstrated that upregulation of ACE2 in liver hepatocellular carcinoma was associated with higher overall survival (hazard ratio, 0.65; p=0.016) and disease-free survival (hazard ratio, 0.66; p=0.007), while overexpression of TMPRSS2 was associated with a 26% reduced risk of death in lung adenocarcinoma (p=0.047) but 50% increased risk of death in breast invasive carcinoma (p=0.015). CONCLUSION: There is a need to take extra precautions for COVID-19 in patients with colorectal cancer, stomach cancer, and lung cancer. Further information on other types of cancer at different stages should be investigated.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , COVID-19/diagnosis , Neoplasms/diagnosis , Neoplasms/genetics , Serine Endopeptidases/genetics , Adenocarcinoma/complications , Adenocarcinoma/diagnosis , Adenocarcinoma/epidemiology , Adenocarcinoma/genetics , Breast Neoplasms/complications , Breast Neoplasms/diagnosis , Breast Neoplasms/epidemiology , Breast Neoplasms/genetics , COVID-19/complications , COVID-19/epidemiology , COVID-19/genetics , Case-Control Studies , Databases as Topic , Female , Gastrointestinal Neoplasms/complications , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/epidemiology , Gastrointestinal Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Genetic Predisposition to Disease , Humans , Liver Neoplasms/complications , Liver Neoplasms/diagnosis , Liver Neoplasms/epidemiology , Liver Neoplasms/genetics , Lung Neoplasms/complications , Lung Neoplasms/diagnosis , Lung Neoplasms/epidemiology , Lung Neoplasms/genetics , Male , Mutation , Neoplasms/complications , Neoplasms/epidemiology , Pandemics , Prognosis , Prostatic Neoplasms/complications , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/genetics , Retrospective Studies , SARS-CoV-2/physiology , Survival Analysis
6.
J Infect ; 83(5): 607-635, 2021 11.
Article in English | MEDLINE | ID: covidwho-1370597
7.
Brief Bioinform ; 22(6)2021 11 05.
Article in English | MEDLINE | ID: covidwho-1254437

ABSTRACT

Despite the association of prevalent health conditions with coronavirus disease 2019 (COVID-19) severity, the disease-modifying biomolecules and their pathogenetic mechanisms remain unclear. This study aimed to understand the influences of COVID-19 on different comorbidities and vice versa through network-based gene expression analyses. Using the shared dysregulated genes, we identified key genetic determinants and signaling pathways that may involve in their shared pathogenesis. The COVID-19 showed significant upregulation of 93 genes and downregulation of 15 genes. Interestingly, it shares 28, 17, 6 and 7 genes with diabetes mellitus (DM), lung cancer (LC), myocardial infarction and hypertension, respectively. Importantly, COVID-19 shared three upregulated genes (i.e. MX2, IRF7 and ADAM8) with DM and LC. Conversely, downregulation of two genes (i.e. PPARGC1A and METTL7A) was found in COVID-19 and LC. Besides, most of the shared pathways were related to inflammatory responses. Furthermore, we identified six potential biomarkers and several important regulatory factors, e.g. transcription factors and microRNAs, while notable drug candidates included captopril, rilonacept and canakinumab. Moreover, prognostic analysis suggests concomitant COVID-19 may result in poor outcome of LC patients. This study provides the molecular basis and routes of the COVID-19 progression due to comorbidities. We believe these findings might be useful to further understand the intricate association of these diseases as well as for the therapeutic development.


Subject(s)
COVID-19/genetics , Diabetes Mellitus/genetics , Hypertension/genetics , Lung Neoplasms/genetics , Myocardial Infarction/genetics , Transcriptome/genetics , ADAM Proteins , COVID-19/virology , Computational Biology , Humans , Interferon Regulatory Factor-7 , Lung Neoplasms/pathology , Membrane Proteins , Myxovirus Resistance Proteins/genetics , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Transcription Factors/genetics
8.
Exp Mol Pathol ; 120: 104634, 2021 06.
Article in English | MEDLINE | ID: covidwho-1152690

ABSTRACT

Lung and colorectal cancers (CRC) have two of the highest mortality rates among all cancer types, and their occurrence and the need for personalized diagnostics and subsequent therapy were not influenced by the COVID-19 pandemics. However, due to the disruption of established delivery chains, standard assays for in vitro diagnostics of those cancers were temporarily not available, forcing us to implement alternative testing methods that enabled at least basic therapy decision making. For this reason, we evaluated rapid testing on the Biocartis Idylla™ platform (Biocartis, Mechelen, Belgium) for four important genes commonly mutated in lung and colorectal cancers, namely EGFR, NRAS, KRAS, and BRAF. Clinical specimens from which the mutation status has previously been determined using Next Generation Sequencing (NGS), were retested to determine whether Idylla™ can offer accurate results. To compare the results, the sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) are calculated for each of the mutation types and then combined to determine the values of the Idylla™ system in total, while setting NGS as the gold-standard basis the assays were compared with. Idylla testing thereby displayed acceptable sensitivity and specificity and delivered reliable results for initial therapy decisions.


Subject(s)
DNA Mutational Analysis/methods , GTP Phosphohydrolases/genetics , High-Throughput Nucleotide Sequencing/methods , Membrane Proteins/genetics , Mutation , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins p21(ras)/genetics , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/virology , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , ErbB Receptors/genetics , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Pandemics , Reproducibility of Results , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Sensitivity and Specificity
10.
Nucleic Acids Res ; 49(7): e37, 2021 04 19.
Article in English | MEDLINE | ID: covidwho-1066376

ABSTRACT

Multiple driver genes in individual patient samples may cause resistance to individual drugs in precision medicine. However, current computational methods have not studied how to fill the gap between personalized driver gene identification and combinatorial drug discovery for individual patients. Here, we developed a novel structural network controllability-based personalized driver genes and combinatorial drug identification algorithm (CPGD), aiming to identify combinatorial drugs for an individual patient by targeting personalized driver genes from network controllability perspective. On two benchmark disease datasets (i.e. breast cancer and lung cancer datasets), performance of CPGD is superior to that of other state-of-the-art driver gene-focus methods in terms of discovery rate among prior-known clinical efficacious combinatorial drugs. Especially on breast cancer dataset, CPGD evaluated synergistic effect of pairwise drug combinations by measuring synergistic effect of their corresponding personalized driver gene modules, which are affected by a given targeting personalized driver gene set of drugs. The results showed that CPGD performs better than existing synergistic combinatorial strategies in identifying clinical efficacious paired combinatorial drugs. Furthermore, CPGD enhanced cancer subtyping by computationally providing personalized side effect signatures for individual patients. In addition, CPGD identified 90 drug combinations candidates from SARS-COV2 dataset as potential drug repurposing candidates for recently spreading COVID-19.


Subject(s)
Algorithms , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Drug Therapy, Combination , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Precision Medicine/methods , Breast Neoplasms/classification , COVID-19/drug therapy , COVID-19/genetics , Datasets as Topic , Drug Repositioning , Drug Synergism , Drug-Related Side Effects and Adverse Reactions , Gene Expression Regulation, Neoplastic/genetics , Genes, Neoplasm/genetics , Humans , Risk Assessment , Workflow
11.
Curr Cancer Drug Targets ; 21(5): 428-442, 2021 07 05.
Article in English | MEDLINE | ID: covidwho-969514

ABSTRACT

BACKGROUND: A higher incidence of COVID-19 infection was demonstrated in cancer patients, including lung cancer patients. This study was conducted to get insights into the enhanced frequency of COVID-19 infection in cancer. METHODS: Using different bioinformatics tools, the expression and methylation patterns of ACE2 and TMPRSS2 were analyzed in healthy and malignant tissues, focusing on lung adenocarcinoma and data were correlated to clinical parameters and smoking history. RESULTS: ACE2 and TMPRSS2 were heterogeneously expressed across 36 healthy tissues with the highest expression levels in digestive, urinary and reproductive organs, while the overall analysis of 72 paired tissues demonstrated significantly lower expression levels of ACE2 in cancer tissues when compared to normal counterparts. In contrast, ACE2, but not TMPRSS2, was overexpressed in LUAD, which inversely correlated to the promoter methylation. This upregulation of ACE2 was age-dependent in LUAD, but not in normal lung tissues. TMPRSS2 expression in non-neoplastic lung tissues was heterogeneous and dependent on sex and smoking history, while it was downregulated in LUAD of smokers. Cancer progression was associated with a decreased TMPRSS2 but unaltered ACE2. In contrast, ACE2 and TMPRSS2 of lung metastases derived from different cancer subtypes was higher than organ metastases of other sites. TMPRSS2, but not ACE2, was associated with LUAD patients' survival. CONCLUSIONS: Comprehensive molecular analyses revealed a heterogeneous and distinct expression and/or methylation profile of ACE2 and TMPRSS2 in healthy lung vs. LUAD tissues across sex, age and smoking history and might have implications for COVID-19 disease.


Subject(s)
COVID-19/epidemiology , COVID-19/genetics , Lung Neoplasms/epidemiology , Lung Neoplasms/genetics , Lung/virology , Adenocarcinoma of Lung/epidemiology , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/virology , Angiotensin-Converting Enzyme 2/genetics , COVID-19/virology , Down-Regulation/genetics , Gene Expression Regulation, Neoplastic/genetics , Humans , Lung Neoplasms/virology , Methylation , Promoter Regions, Genetic/genetics , SARS-CoV-2/pathogenicity , Serine Endopeptidases/genetics , Smoking/adverse effects , Up-Regulation/genetics
12.
Oncology (Williston Park) ; 34(8): 302-304, 2020 Aug 12.
Article in English | MEDLINE | ID: covidwho-859473
13.
Genomics ; 112(6): 4912-4923, 2020 11.
Article in English | MEDLINE | ID: covidwho-752713

ABSTRACT

COVID-19 is a pandemic that began to spread worldwide caused by SARS-CoV-2. Lung cancer patients are more susceptible to SARS-CoV-2 infection. The SARS-CoV-2 enters into the host by the ACE2 receptor. Thus, ACE2 is the key to understand the mechanism of SARS-CoV-2 infection. However, the lack of knowledge about the biomarker of COVID-19 warrants the development of ACE2 biomarkers. The analysis of ACE2 expression in lung cancer was performed using The Cancer Genome Atlas (TCGA). Therefore, we investigated the prognosis, clinical characteristics, and mutational analysis of lung cancer. We also analyzed the shared proteins between the COVID-19 and lung cancer, protein-protein interactions, gene-miRNAs, gene-transcription factors (TFs), and the signaling pathway. Finally, we compared the mRNA expression of ACE2 and its co-expressed proteins using the TCGA. The up-regulation of ACE2 in lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) was found irrespective of gender and age. We found the low survival rate in high expression of ACE2 in lung cancer patients and 16 mutational positions. The functional assessment of targeted 12,671, 3107, and 29 positive genes were found in COVID-19 disease, LUAD, and LUSC, respectively. Then, we identified eight common genes that interact with 20 genes, 219 miRNAs, and 16 TFs. The common genes performed the mRNA expression in lung cancer, which proved the ACE2 is the best potential biomarker compared to co-expressed genes. This study uncovers the relationship between COVID-19 disease and lung cancer. We identified ACE2 and also its co-expressed proteins are the potential biomarker and therapy as the current COVID-19 disease and lung cancer.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , COVID-19/genetics , Lung Neoplasms/pathology , Lung Neoplasms/virology , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/mortality , Adenocarcinoma of Lung/pathology , Adult , Aged , Aged, 80 and over , Biomarkers , Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Computational Biology/methods , Female , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/genetics , Lung Neoplasms/mortality , Male , MicroRNAs , Middle Aged , Mutation , Protein Interaction Maps/genetics , Young Adult
14.
J Med Virol ; 92(11): 2637-2647, 2020 11.
Article in English | MEDLINE | ID: covidwho-505910

ABSTRACT

Recent days have seen growing evidence of cancer's susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and of the effect of genomic differences on the virus' entrance genes in lung cancer. Genetic confirmation of the hypotheses regarding gene expression and mutation pattern of target genes, including angiotensin-converting enzyme-2 (ACE2), transmembrane serine protease 2 (TMPRSS2), basigin (CD147/BSG) and paired basic amino acid cleaving enzyme (FURIN/PCSK3), as well as correlation analysis, was done in relation to lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) using in silico analysis. Not only were gene expression and mutation patterns detected, but also there were correlation and survival analysis between ACE2 and other target genes expression levels. The total genetic anomaly carrying rate of target genes, including ACE2, TMPRSS2, CD147/BSG, and FURIN/PCSK3, was determined as 8.1% and 21 mutations were detected, with 7 of these mutations having pathogenic features. p.H34N on the RBD binding residues for SARS-CoV-2 was determined in our LUAD patient group. According to gene expression analysis results, though the TMPRSS2 level was statistically significantly decreased in the LUSC patient group compared to healthy control, the ACE2 level was determined to be high in LUAD and LUSC groups. There were no meaningful differences in the expression of CD147 and FURIN genes. The challenge for today is building the assessment of genomic susceptibility to COVID-19 in lung cancer, requiring detailed experimental laboratory studies, in addition to in silico analyses, as a way of assessing the mechanism of novel virus invasion that can be used in the development of effective SARS-CoV-2 therapy.


Subject(s)
COVID-19/virology , Gene Expression , Host-Pathogen Interactions/genetics , Lung Neoplasms/genetics , Mutation , Adenocarcinoma of Lung/genetics , Adult , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2/genetics , Basigin/genetics , Carcinoma, Squamous Cell/genetics , Computer Simulation , Female , Furin/genetics , Humans , Lung Neoplasms/complications , Lung Neoplasms/virology , Male , Middle Aged , SARS-CoV-2/physiology , Serine Endopeptidases/genetics , Virus Internalization
15.
Mol Cancer ; 19(1): 80, 2020 04 28.
Article in English | MEDLINE | ID: covidwho-133383

ABSTRACT

Recent studies have reported that COVID-19 patients with lung cancer have a higher risk of severe events than patients without cancer. In this study, we investigated the gene expression of angiotensin I-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) with prognosis in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Lung cancer patients in each age stage, subtype, and pathological stage are susceptible to SARS-CoV-2 infection, except for the primitive subtype of LUSC. LUAD patients are more susceptible to SARS-CoV-2 infection than LUSC patients. The findings are unanimous on tissue expression in gene and protein levels.


Subject(s)
Adenocarcinoma of Lung/complications , Betacoronavirus , Carcinoma, Squamous Cell/complications , Coronavirus Infections/etiology , Lung Neoplasms/complications , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/etiology , Serine Endopeptidases/genetics , Adenocarcinoma of Lung/genetics , Angiotensin-Converting Enzyme 2 , Animals , COVID-19 , Carcinoma, Squamous Cell/genetics , Cell Line , Coronavirus Infections/genetics , Disease Susceptibility , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/genetics , Mice , Mice, Transgenic , Pandemics , Peptidyl-Dipeptidase A/biosynthesis , Pneumonia, Viral/genetics , SARS-CoV-2 , Serine Endopeptidases/biosynthesis
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