Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Detecting lung tumors from circulating microRNA profiles

ABSTRACT: We aimed to determine if lung cancer detection can be improved by circulating miRNAs as biomarkers. To this end, we collected blood of over 3000 individuals using PAXgene blood tubes. The individuals were diagnosed with lung cancer (LCa), a non-tumor lung disease (NTLD), another disease (OD) or were healthy controls. For every individual we determined their miRNA expression patterns. Total RNA was extracted with Qiagen PAXgene Blood miRNA Kit, labeled and hybridized with the Agilent miRNA Complete Labeling and Hyb Kit and scanned with Agilent microarray scanner system.

ORGANISM(S): Homo sapiens

SUBMITTER: Tobias Fehlmann

PROVIDER: E-MTAB-8026 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Evaluating the Use of Circulating MicroRNA Profiles for Lung Cancer Detection in Symptomatic Patients.

Fehlmann Tobias T Kahraman Mustafa M Ludwig Nicole N Backes Christina C Galata Valentina V Keller Verena V Geffers Lars L Mercaldo Nathaniel N Hornung Daniela D Weis Tanja T Kayvanpour Elham E Abu-Halima Masood M Deuschle Christian C Schulte Claudia C Suenkel Ulrike U von Thaler Anna-Katharina AK Maetzler Walter W Herr Christian C Fähndrich Sebastian S Vogelmeier Claus C Guimaraes Pedro P Hecksteden Anne A Meyer Tim T Metzger Florian F Diener Caroline C Deutscher Stephanie S Abdul-Khaliq Hashim H Stehle Ingo I Haeusler Sebastian S Meiser Andreas A Groesdonk Heinrich V HV Volk Thomas T Lenhof Hans-Peter HP Katus Hugo H Balling Rudi R Meder Benjamin B Kruger Rejko R Huwer Hanno H Bals Robert R Meese Eckart E Keller Andreas A

JAMA oncology 20200501 5

<h4>Importance</h4>The overall low survival rate of patients with lung cancer calls for improved detection tools to enable better treatment options and improved patient outcomes. Multivariable molecular signatures, such as blood-borne microRNA (miRNA) signatures, may have high rates of sensitivity and specificity but require additional studies with large cohorts and standardized measurements to confirm the generalizability of miRNA signatures.<h4>Objective</h4>To investigate the use of blood-bor ...[more]

PMID: 32134442

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Project description:Seventh generation Exiqon locked nucleic acid miRCURY LNA microarrays were used to profile the expression of microRNAs in whole blood of patients with lung cancer and of clinically relevant controls without the disease (individuals with non-cancerous lung nodule, at high risk for cancer because of heavy smoking, or with lung cancer treated by surgical resection). The goal was to examine if whole blood microRNAs can be used for developing a non-invasive assay to diagnose lung cancer. Using the PAXgene Blood miRNA kit (Qiagen, Valencia, CA, USA), total RNA was isolated from whole blood stabilized and stored in PAXgene Blood RNA tubes for 85 individuals with lung cancer, 59 individuals without the disease but at a high risk for the disease because of smoking, and 17 individuals with a non-cancerous pulmonary nodule. RNA was also isolated from 13 samples of blood of 12 of the lung cancer cases following surgery; blood samples were collected on two different days post-operatively for one of the cases (Sample names 157 and 160). The data-set here includes data (sample name 171) from a post-operative blood sample of an individual (who had the lung cancer removed by operation) for whom good array data was not obtained for RNA from a pre-operative blood sample. Two RNA samples were used to test technical duplicability of the microarray platform (pairs of sample names 59 & 192, and 175 & 182). Thus, a total of 162 unique individuals and 175 unique RNA samples are covered by this data-set. Isolated RNA was provided to Exiqon (Denmark) for microRNA quantification using microarrays. Quality and concentration of RNA in the samples was assessed by Nanodrop 2000 (Thermo Scientific, Wilmington, DE, USA) and Bioanalyzer 2100 (Agilent, Santa Clara, CA, USA) instruments. Sample RNA (500 ng) was labeled with the Cy3-like Hy3 dye, mixed with 500 ng of a human universal reference RNA (product number AM6000, Ambion, Austin, TX, USA) that was labeled with the Cy5-like Hy5 dye, and hybridized to 7th generation miRCURY locked nucleic acid oligonucleotide microarrays. Sixty-two artificial small RNAs were spiked-in each RNA sample before labeling. disease state: Lung cancer (before surgical resection of lung cancer): 1, 2, 4, 5, 6, 7, 8, 9, 10, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 61, 63, 64, 65, 67, 68, 69, 70, 81, 82, 85, 86, 87, 88, 89, 90, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 121, 122, 123, 124, 125, 126, 127, 149, 151, 153, 154, 156, 158, 165, 167, 174, 175, 176, 177, 179, 180, 181, 183, 184, 186, 187, 188, 189, 193 disease state: Non-cancerous lung nodule: 128, 129, 130, 131, 133, 134, 135, 136, 137, 140, 141, 142, 144, 145, 146, 148, 182, 190 disease state: None (after surgical resection of lung cancer): 155, 157, 159, 160, 161, 162, 163, 164, 166, 169, 170, 171, 172, 173 disease state: None (no current or past lung cancer or non-cancerous nodule): 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 113, 114, 115, 116, 117, 118, 119, 120, 192 individual: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162

Project description:Introduction: Diagnosis of severe influenza pneumonia remains challenging because of the lack of correlation between presence of influenza virus and patient’s clinical status. We conducted gene expression profiling in the whole blood of critically ill patients to identify a gene signature that would allow clinicians to distinguish influenza infection from other causes of severe respiratory failure (e.g. bacterial pneumonia, non-infective systemic inflammatory response syndrome). Methods: Whole blood samples were collected from critically ill individuals and assayed on Illumina HT-12 gene expression beadarrays. Differentially expressed genes were determined by linear mixed model analysis and over-represented biological pathways determined using GeneGo MetaCore. Results: The gene expression profile of H1N1 influenza A pneumonia was distinctly different from bacterial pneumonia and systemic inflammatory response syndrome. The influenza gene expression profile is characterized by up-regulation of genes from cell cycle regulation, apoptosis and DNA-damage response pathways. In contrast, no distinctive gene-expression signature was found in patients with bacterial pneumonia or systemic inflammatory response syndrome. The gene expression profile of influenza infection persisted through five days of follow-up. Furthermore, in patients with primary H1N1 influenza A infection who subsequently developed bacterial co-infection, the influenza gene-expression signature remained unaltered, despite the presence of a super-imposed bacterial infection. Conclusions: The whole blood expression profiling data indicates that the host response to influenza pneumonia is distinctly different from that caused by bacterial pathogens. This information may speed up identification of the cause of infection in patients presenting with severe respiratory failure, allowing appropriate patient care to be undertaken more rapidly. Daily PAXgene samples for up to 5 days for; influenza A pneumonia patients (n=8), bacterial pneumonia patients (n=16), mixed bacterial and influenza A pneumonia patients (n=3), systemic inflammatory response patients (SIRS, n=13). Days 1 and 5 PAXgene samples for healthy control individuals

Project description:The Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez Palacio, Mexico was recently established to better understand the impacts of prenatal exposure to inorganic arsenic (iAs). In this study, we examined a subset (n = 40) of newborn cord blood samples for microRNA (miRNA) expression changes associated with in utero arsenic exposure. Levels of iAs in maternal drinking water (DW-iAs) and maternal urine were assessed. Levels of DW-iAs ranged from below detectable values to 236 µg/L (mean = 51.7 µg/L). Total arsenic in maternal urine (U-tAs) was defined as the sum of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) and ranged from 6.2 to 319.7 µg/L (mean = 64.5 µg/L). Genome-wide miRNA expression analysis of cord blood revealed 12 miRNAs with increasing expression associated with U-tAs. Transcriptional targets of the miRNAs were computationally predicted and subsequently assessed using transcriptional profiling. Pathway analysis demonstrated that the U-tAs-associated miRNAs are involved in signaling pathways related to known health outcomes of iAs exposure including cancer and diabetes mellitus. Immune response-related mRNAs were also identified with decreased expression levels associated with U-tAs, and predicted to be mediated in part by the arsenic-responsive miRNAs. Results of this study highlight miRNAs as novel responders to prenatal arsenic exposure that may contribute to associated immune response perturbations. We assessed the impact of prenatal exposure to arsenic on genome-wide miRNA expression profiles and their potential influence on gene expression patterns in the Biomarkers of Exposure to ARsenic (BEAR) prospective pregnancy cohort. This cohort includes residents from Gómez Palacio, located in the state of Durango in the Lagunera region of Northern Mexico. A total of 200 pregnant women residing in Gómez Palacio, State of Durango, Mexico, were recruited at the General Hospital of Gómez Palacio to participate in the BEAR prospective pregnancy cohort. The present study focuses on miRNA expression profiles and utilizes 40 samples obtained from mother-newborn pairs selected from the larger cohort (n=200). The subcohort was selected to include subjects exposed to varying levels of arsenic as determined by both total arsenic in maternal urine (U-tAs) and inorganic arsenic in drinking water (DW-iAs). Cord blood samples were collected from the newborns immediately after infant delivery. Blood samples were collected using PreAnalytix PaxGene RNA tubes and extracted using the PAXgene RNA Kit, per standard protocol (Qiagen, Valencia, CA). Isolated RNA used for microarray analysis were amplified and labeled using the NuGEN Ovation Pico WTA System V2 and Encore Biotin Module, respectively (NuGEN, San Carlos, CA). RNA isolated from 40 cord blood samples were labeled and hybridized to the Agilent Human miRNA Microarray, based off miRBase v16.0.

Dataset Information

Detecting lung tumors from circulating microRNA profiles

Publications

Evaluating the Use of Circulating MicroRNA Profiles for Lung Cancer Detection in Symptomatic Patients.

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