ENA0000GenomicsMultiomicsCrystal, Department of Genetic Medicine, Weill Cornell Medical Collegehttps://www.ebi.ac.uk/ena/browser/view/PRJNA128993Homo sapiens<![CDATA[Cystatin A (gene: CSTA), is up-regulated in non-small-cell lung cancer (NSCLC) and dysplastic vs normal human bronchial epithelium. In the context that chronic obstructive pulmonary disease (COPD), a small airway epithelium (SAE) disorder, is independently associated with NSCLC (especially squamous cell carcinoma, SCC), but only occurs in a subset of smokers, we hypothesized that genetic variation, smoking and COPD modulate CSTA gene expression levels in SAE, with further up-regulation in SCC. Gene expression was assessed by microarray in SAE of 178 individuals [healthy nonsmokers (n=60), healthy smokers (n=82), and COPD smokers (n=36)], with corresponding large airway epithelium (LAE) data in a subset (n=52). Blood DNA was genotyped by SNP microarray. Twelve SNPs upstream of the CSTA gene were all significantly associated with CSTA SAE gene expression (p<0.04 to 5 x 10-4). CSTA gene expression levels in SAE were higher in COPD smokers (28.4 ± 2.0) than healthy smokers (19.9 ± 1.4, p<10-3), who in turn had higher levels than nonsmokers (16.1 ± 1.1, p<0.04). CSTA LAE gene expression was also smoking-responsive (p<10-3). Using comparable publicly available NSCLC expression data, CSTA was up-regulated in SCC vs LAE (p<10-2) and down-regulated in adenocarcinoma vs SAE (pENAhuman being, Smoking Behavior, respiratory epithelium, DISEASE (COPD), Chronic Airflow Obstructions, malignant lung tumor, lung cancer, CAO - Chronic airflow obstruction, malignant tumor of lung, chronic obstructive pulmonary disease (COPD), CHRONIC OBSTRUCTIVE PULM DIS, malignant neoplasm of the lung, Chronic obstructive pulmonary disease NOS, autosomal dominant, Chronic obstructive pulmonary disease finding, PULMONARY DISEASE (COPD), Pulmonary Disease, chronic obstructive airways disease NOS (disorder), Chronic irreversible airway obstruction, Chronic Obstructive Pulmonary Disease (COPD), COLD (chronic obstructive lung disease), malignant tumour of the lung, NEC in ICD9CM_2006, alveolar cell carcinoma, LNCR, CAFL - Chronic airflow limitation, Chronic Obstructive, man, Genotypes, Chronic airflow limitation, resistance to, Smoking Habits, disease (COPD), malignant neoplasm of lung, NEC, epithelium of respiratory tract, Habit, Chronic, Behaviors, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, somatic mutation, COPD, epithelial tissue of respiratory tract, CHRONIC, COAD - Chronic obstructive airways disease, chronic obstructive lung disease [Ambiguous], obstructive lung disease, airway epithelium, chronic obstructive airways disease NOS, not elsewhere classified, respiratory tract epithelial tissue, COAD, Epidermal SH Protease Inhibitor, Stefin A, Epidermal SH-Protease Inhibitor, COLD - Chronic obstructive lung disease, somatic, Behavior, chronic, PULM DIS CHRONIC OBSTRUCTIVE, Airflow Obstructions, Chronic obstructive pulmonary disease finding (finding), CHRONIC OBSTRUCTIVE AIRWAY DIS, pulmonary disease (COPD), Genogroup, cancer of lung, CHRONIC OBSTRUCTIVE, Smoking Habit, chronic obstructive pulmonary disease and allied conditions, Nonsmall cell lung cancer, malignant lung tumour, Chronic airway disease, NOS, malignant tumour of lung, (COPD), chronic airway obstruction, Airflow Obstruction, chronic obstructive, CAL - Chronic airflow limitation, COPD NOS, Smoking, CHRONIC OBSTRUCTIVE LUNG DIS, chronic obstructive airway disease, Chronic Obstructive Airways Disease, Chronic airway obstruction, Chronic obstructive lung disease, malignant tumor of the lung, malignant lung neoplasm, cold, Dops, adenocarcinoma of lung, susceptibility to, somatic., human, Chronic Airflow Obstruction, response to tyrosine kinase inhibitor in, Genogroups, nonsmall cell lung cancer, OBSTRUCTIVE PULMONARY DISEASE (COPD), COPD - Chronic obstructive pulmonary disease, Smoking Behaviors, chronic obstructive lung disease (disorder), chronic obstructive airways disease, protection against, cold (chronic obstructive lung disease), Chronic Obstructive Lung Disease, obstructive pulmonary disease (COPD), lung neoplasm, COLD, chronic obstructive lung disease, Habits, chronic obstructive pulmonary diseasehuman being, human., man0.00.00.00.00.00falseHomo sapiensModulation of Cystatin A Expression in Human Airway Epithelium Related to Genotype, Smoking COPD and Lung Cancer2022-05-122014-02-11PRJNA128993GSE22047213254299606