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1.
Zhongguo Fei Ai Za Zhi ; 25(3): 147-155, 2022 Mar 20.
Article in Chinese | MEDLINE | ID: covidwho-1780097

ABSTRACT

BACKGROUND: At present, the research progress of targeted therapy for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) gene mutations in lung adenocarcinoma is very rapid, which brings new hope for the treatment of advanced lung adenocarcinoma patients. However, the specific imaging and pathological features of EGFR and ALK gene mutations in adenocarcinoma are still controversial. This study will further explore the correlation between EGFR, ALK gene mutations and imaging and pathological features in invasive lung adenocarcinoma. METHODS: A total of 525 patients with lung adenocarcinoma who underwent surgery in our center from January 2018 to December 2019 were included. According to the results of postoperative gene detection, the patients were divided into EGFR gene mutation group, ALK gene mutation group and wild group, and the EGFR gene mutation group was divided into exon 19 and exon 21 subtypes. The pathological features of the mutation group and wild group, such as histological subtype, lymph node metastasis, visceral pleural invasion (VPI) and imaging features such as tumor diameter, consolidation tumor ratio (CTR), lobulation sign, spiculation sign, pleural retraction sign, air bronchus sign and vacuole sign were analyzed by univariate analysis and multivariate Logistic regression analysis to explore whether the gene mutation group had specific manifestations. RESULTS: EGFR gene mutation group was common in women (OR=2.041, P=0.001), with more pleural traction sign (OR=1.506, P=0.042), and had little correlation with lymph node metastasis and VPI (P>0.05). Among them, exon 21 subtype was more common in older (OR=1.022, P=0.036), women (OR=2.010, P=0.007), and was associated with larger tumor diameter (OR=1.360, P=0.039) and pleural traction sign (OR=1.754, P=0.029). Exon 19 subtype was common in women (OR=2.230, P=0.009), with a high proportion of solid components (OR=1.589, P=0.047) and more lobulation sign (OR=2.762, P=0.026). ALK gene mutations were likely to occur in younger patients (OR=2.950, P=0.045), with somking history (OR=1.070, P=0.002), and there were more micropapillary components (OR=4.184, P=0.019) and VPI (OR=2.986, P=0.034) in pathology. CONCLUSIONS: The EGFR and ALK genes mutated adenocarcinomas have specific imaging and clinicopathological features, and the mutations in exon 19 or exon 21 subtype have different imaging features, which is of great significance in guiding the clinical diagnosis and treatment of pulmonary nodules.


Subject(s)
Adenocarcinoma of Lung , Anaplastic Lymphoma Kinase , Lung Neoplasms , Adenocarcinoma of Lung/diagnostic imaging , Adenocarcinoma of Lung/genetics , Aged , Anaplastic Lymphoma Kinase/genetics , ErbB Receptors/genetics , Female , Genes, erbB-1 , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Mutation , Tomography, X-Ray Computed/methods
2.
Chem Biol Interact ; 353: 109796, 2022 Feb 01.
Article in English | MEDLINE | ID: covidwho-1611644

ABSTRACT

Coronavirus disease 2019 (COVID-19) was declared a serious global public health emergency. Hospitalization and mortality rates of lung cancer patients diagnosed with COVID-19 are higher than those of patients presenting with other cancers. However, the reasons for the outcomes being disproportionately severe in lung adenocarcinoma (LUAD) patients with COVID-19 remain elusive. The present study aimed to identify the possible causes for disproportionately severe COVID-19 outcomes in LUAD patients and determine a therapeutic target for COVID-19 patients with LUAD. We used publicly available data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and various bioinformatics tools to identify and analyze the genes implicated in SARS-CoV-2 infection in LUAD patients. Upregulation of the SARS-CoV-2 infection-related molecules dipeptidyl peptidase 4, basigin, cathepsin B (CTSB), methylenetetrahydrofolate dehydrogenase, and peptidylprolyl isomerase B rather than angiotensin-converting enzyme 2 may explain the relatively high susceptibility of LUAD patients to SARS-CoV-2 infection. CTSB was highly expressed in the LUAD tissues after SARS-CoV-2 infection, and its expression was positively correlated with immune cell infiltration and proinflammatory cytokine expression. These findings suggest that CTSB plays a vital role in the hyperinflammatory response in COVID-19 patients with LUAD and is a promising target for the development of a novel drug therapy for COVID-19 patients.


Subject(s)
Adenocarcinoma of Lung/virology , COVID-19/genetics , Cathepsin B/genetics , Lung Neoplasms/virology , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/immunology , Adenocarcinoma of Lung/mortality , Angiotensin-Converting Enzyme 2/genetics , Animals , Basigin/genetics , CD8-Positive T-Lymphocytes/virology , COVID-19/immunology , COVID-19/mortality , Cricetinae , Cyclophilins/genetics , Cytokines/blood , Dipeptidyl Peptidase 4/genetics , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/genetics , Lung Neoplasms/immunology , Lung Neoplasms/mortality , Methylenetetrahydrofolate Dehydrogenase (NADP)/genetics , Minor Histocompatibility Antigens/genetics , Molecular Targeted Therapy , Prognosis , Protein Interaction Maps/genetics , Up-Regulation
3.
Environ Sci Pollut Res Int ; 29(15): 22012-22030, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1514070

ABSTRACT

Coronavirus disease 2019 (COVID-19) continues as a global pandemic. Patients with lung cancer infected with COVID-19 may develop severe disease or die. Treating such patients severely burdens overwhelmed healthcare systems. Here, we identified potential pathological mechanisms shared between patients with COVID-19 and lung adenocarcinoma (LUAD). Co-expressed, differentially expressed genes (DEGs) in patients with COVID-19 and LUAD were identified and used to construct a protein-protein interaction (PPI) network and to perform enrichment analysis. We used the NetworkAnalyst platform to establish a co-regulatory of the co-expressed DEGs, and we used Spearman's correlation to evaluate the significance of associations of hub genes with immune infiltration and immune checkpoints. Analysis of three datasets identified 112 shared DEGs, which were used to construct a protein-PPI network. Subsequent enrichment analysis revealed co-expressed genes related to biological process (BP), molecular function (MF), and cellular component (CC) as well as to pathways, specific organs, cells, and diseases. Ten co-expressed hub genes were employed to construct a gene-miRNA, transcription factor (TF)-gene, and TF-miRNA network. Hub genes were significantly associated with immune infiltration and immune checkpoints. Finally, methylation level of hub genes in LUAD was obtained via UALCAN database. The present multi-dimensional study reveals commonality in specific gene expression by patients with COVID-19 and LUAD. These findings provide insights into developing strategies for optimising the management and treatment of patients with LUAD with COVID-19.


Subject(s)
Adenocarcinoma of Lung , COVID-19 , Lung Neoplasms , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/metabolism , Adenocarcinoma of Lung/pathology , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , COVID-19/genetics , Computational Biology/methods , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/pathology
4.
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
5.
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
6.
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
7.
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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