Quantitative analysis of a novel DNA hypermethylation panel using bronchial specimen for lung cancer diagnosis
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ABSTRACT:
PROVIDER: EGAD00010002465 | EGA |
REPOSITORIES: EGA
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Project description:This dataset includes an analyzed DMP file that provide the information about differential methylation positions based on Illumina Infinium MethylationEPIC BeadChip. All samples (5 lung cancer cases vs. 5 benign lung disease controls) were obtained from bronchial washings at the site of the lesion under bronchoscopy manipulation. Of the five lung cancer cases, 3 are adenocarcinoma and 2 are squamous carcinoma.
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Project description:Non-diagnostic findings in Transbronchial Lung Biopsy (TBLB) and Endobronchial Ultrasound-guided Transbronchial Lung Biopsy (EBUS-TBLB) are not uncommon. A challenge is to improve lung cancer detection by TBLB/EBUS-TBLB. In order to improve the diagnostic yield of bronchoscopy, we used 850K methylation chip to identify methylation sites that distinguish malignant from benign lung nodules.We found that the combination of HOXA7, SHOX2,and SCT methylation analysis has the best diagnostic yield in 123 bronchial washing (sensitivity: 74·1%; AUC: 0·851) and 172 brushing samples (sensitivity: 86·1%; AUC: 0·915). We developed a kit comprising these three genes and validated the kit in 329 unique bronchial washing samples, 397 unique brushing samples, and 179 unique patients with both washing and brushing samples. The diagnostic accuracy of the panel alone in lung cancer diagnosis was 86·9%, 91·2% and 95% in bronchial washing, brushing, and washing+brushing samples, respectively. The panel's sensitivity in combination with cytology, rapid on-site evaluation (ROSE), and histology in lung cancer diagnosis was 90·8% and 95.8% in bronchial washing and brushing samples, respectively, and 100% in washing+brushing samples. Quantitative analysis of the three-gene panel improves lung cancer diagnosis by bronchoscopy.
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2021-09-02 | GSE171424 | GEO
Project description:Prior microarray studies of smokers at high risk for lung cancer have demonstrated that heterogeneity in bronchial airway epithelial cell gene expression response to smoking can serve as an early diagnostic biomarker for lung cancer. This study examines the relationship between gene expression variation and genetic variation in a central molecular pathway (NRF2-mediated antioxidant response) associated with smoking exposure and lung cancer. We assessed global gene expression in histologically normal airway epithelial cells obtained at bronchoscopy from smokers who developed lung cancer (SC, n=20), smokers without lung cancer (SNC, n=24), and never smokers (NS, n=8). Functional enrichment showed that the NRF2-mediated antioxidant response pathway differed significantly among these groups. Keywords: Global mRNA expression profiling
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Project description:Using primary human bronchial epithelial cells collected at bronchoscopy, we have perturbed signaling pathways important in regulation of response to tobacco smoke exposure and cancer development: ATM, BCL2, GPX1, NOS2, IKBKB, and SIRT1 Using gene expression profiles generated for each pathway and four independent gene expression datasets, we show that SIRT1 activity is significantly up-regulated in cytologically normal airway epithelial cells from active smokers compared to non-smokers; and in contrast, this activity is strikingly down-regulated in non-small cell lung cancer.
2012-09-27 | GSE37058 | GEO
Project description:Prior microarray studies of smokers at high risk for lung cancer have demonstrated that heterogeneity in bronchial airway epithelial cell gene expression response to smoking can serve as an early diagnostic biomarker for lung cancer. This study examines the relationship between gene expression variation and genetic variation in a central molecular pathway (NRF2-mediated antioxidant response) associated with smoking exposure and lung cancer. We assessed global gene expression in histologically normal airway epithelial cells obtained at bronchoscopy from smokers who developed lung cancer (SC, n=20), smokers without lung cancer (SNC, n=24), and never smokers (NS, n=8). Functional enrichment showed that the NRF2-mediated antioxidant response pathway differed significantly among these groups. Keywords: Global mRNA expression profiling 21 total arrays (20 unique patients) run on total RNA obtained from Bronchial Epithelium of Smokers with Lung Cancer 30 total arrays (24 unique patients) run on total RNA obtained from Bronchial Epithelium of Smokers without Lung Cancer 9 total arrays (8 unique patients) run on total RNA obtained from Bronchial Epithelium of Never Smokers
2010-09-30 | E-GEOD-19027 | biostudies-arrayexpress
Project description:BACKGROUND: In patients with suspicious pulmonary lesions, bronchoscopy is frequently non-diagnostic. This often results in additional invasive testing, including surgical biopsy, although many patients have benign disease. We sought to validate an airway gene-expression classifier for lung cancer in patients undergoing diagnostic bronchoscopy. METHODS: Two multicenter prospective studies (AEGIS 1 and 2) enrolled 1357 current or former smokers undergoing bronchoscopy for suspected lung cancer. Bronchial epithelial cells were collected from normal appearing mucosa in the mainstem bronchus during bronchoscopy. Patients without a definitive diagnosis from bronchoscopy were followed for 12 months. A gene-expression classifier was used to assess the risk of lung cancer, and its performance was evaluated. RESULTS: A total of 298 patients from AEGIS 1 and 341 from AEGIS 2 met criteria for analysis. Bronchoscopy was non-diagnostic for cancer in 272 of 639 patients (43%; 95%CI, 39-46%). The gene expression classifier correctly identified 431 of 487 patients with cancer (89% sensitivity; 95%CI, 85-91%), and 72 of 152 patients without cancer (47% specificity; 95%CI, 40-55%). The combination of the classifier and bronchoscopy had a sensitivity of 97% (95%CI, 95-98%), which was independent of size, location, stage, and histological subtype of lung cancer. In patients with an intermediate pre-test risk (10-60%) of lung cancer, the NPV of the classifier was 91% (95%CI 75-98%). CONCLUSIONS: In patients with an intermediate risk of lung cancer and a non-diagnostic bronchoscopy, a gene-expression classification of “low-risk” warrants consideration of a more conservative diagnostic approach that could reduce unnecessary invasive testing in patients with benign disease.
2015-05-17 | GSE66499 | GEO
Project description:BACKGROUND: In patients with suspicious pulmonary lesions, bronchoscopy is frequently non-diagnostic. This often results in additional invasive testing, including surgical biopsy, although many patients have benign disease. We sought to validate an airway gene-expression classifier for lung cancer in patients undergoing diagnostic bronchoscopy. METHODS: Two multicenter prospective studies (AEGIS 1 and 2) enrolled 1357 current or former smokers undergoing bronchoscopy for suspected lung cancer. Bronchial epithelial cells were collected from normal appearing mucosa in the mainstem bronchus during bronchoscopy. Patients without a definitive diagnosis from bronchoscopy were followed for 12 months. A gene-expression classifier was used to assess the risk of lung cancer, and its performance was evaluated. RESULTS: A total of 298 patients from AEGIS 1 and 341 from AEGIS 2 met criteria for analysis. Bronchoscopy was non-diagnostic for cancer in 272 of 639 patients (43%; 95%CI, 39-46%). The gene expression classifier correctly identified 431 of 487 patients with cancer (89% sensitivity; 95%CI, 85-91%), and 72 of 152 patients without cancer (47% specificity; 95%CI, 40-55%). The combination of the classifier and bronchoscopy had a sensitivity of 97% (95%CI, 95-98%), which was independent of size, location, stage, and histological subtype of lung cancer. In patients with an intermediate pre-test risk (10-60%) of lung cancer, the NPV of the classifier was 91% (95%CI 75-98%). CONCLUSIONS: In patients with an intermediate risk of lung cancer and a non-diagnostic bronchoscopy, a gene-expression classification of “low-risk” warrants consideration of a more conservative diagnostic approach that could reduce unnecessary invasive testing in patients with benign disease. 680 CEL files from 639 BEC specimens, 152 benign and 487 malignant samples
2015-05-17 | E-GEOD-66499 | biostudies-arrayexpress
Project description:MicroRNA expression was assayed from bronchial epithelial cells collected via bronchoscopy from healthy current and never smoker volunteers in order to determine the effect of cigarette smoke exposure on airway epithelial microRNA expression Keywords: Global microRNA expression profiling Bronchial epithelial cells were collected from current and never smokers via bronchoscopy. Low molecular weight RNA ( < 200 nucleotides) was isolated and hybridized to Invitrogen NCode microRNA microarrays to determine which microRNAs detected in bronchial epithelial cells were differentially expressed in the airways of smokers.
2009-01-28 | E-GEOD-14634 | biostudies-arrayexpress