Malignant mesothelioma EWAS on European prospective study
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ABSTRACT:
PROVIDER: EGAS00001006432 | EGA |
REPOSITORIES: EGA
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Project description:Malignant Pleural Mesothelioma (MPM) is an aggressive cancer that is often diagnosed at an advanced stage and is characterized by a long latency period (20-40 years between initial exposure and diagnosis) and prior exposure to asbestos. Currently accurate diagnosis of MPM is difficult due to the lack of sensitive biomarkers, and despite minor improvements in treatment, median survival rates do not exceed 12 months. Accumulating evidence suggests that aberrant expression of long non-coding RNAs (lncRNAs) play an important functional role in cancer biology. LncRNAs are a class of recently discovered non-protein coding RNAs >200 nucleotides in length with a role in regulating transcription. Here we used NCode long noncoding microarrays to identify differentially expressed lncRNAs potentially involved in MPM pathogenesis. High priority candidate lncRNAs were selected on the basis of statistical (P<0.05) and biological significance (>3-fold difference). Expression levels of 9 candidate lncRNAs were technically validated using RT-qPCR, and biologically validated in three independent test sets: (1) 57 archived MPM tissues obtained from extrapleural pneumonectomy patients, (2) 15 cryopreserved MPM and 3 benign pleura, and (3) an extended panel of 10 MPM cell lines. RT-qPCR analysis demonstrated consistent up-regulation of these lncRNAs in independent datasets. ROC curve analysis showed that two candidates were able to separate benign pleura and MPM with high sensitivity and specificity, and were associated with nodal metastases and survival following induction chemotherapy. These results suggest that lncRNAs have potential to serve as biomarkers in MPM.
2013-08-22 | GSE48174 | GEO
Project description:Malignant Pleural Mesothelioma (MPM) is an aggressive cancer that is often diagnosed at an advanced stage and is characterized by a long latency period (20-40 years between initial exposure and diagnosis) and prior exposure to asbestos. Currently accurate diagnosis of MPM is difficult due to the lack of sensitive biomarkers, and despite minor improvements in treatment, median survival rates do not exceed 12 months. Accumulating evidence suggests that aberrant expression of long non-coding RNAs (lncRNAs) play an important functional role in cancer biology. LncRNAs are a class of recently discovered non-protein coding RNAs >200 nucleotides in length with a role in regulating transcription. Here we used NCode long noncoding microarrays to identify differentially expressed lncRNAs potentially involved in MPM pathogenesis. High priority candidate lncRNAs were selected on the basis of statistical (P<0.05) and biological significance (>3-fold difference). Expression levels of 9 candidate lncRNAs were technically validated using RT-qPCR, and biologically validated in three independent test sets: (1) 57 archived MPM tissues obtained from extrapleural pneumonectomy patients, (2) 15 cryopreserved MPM and 3 benign pleura, and (3) an extended panel of 10 MPM cell lines. RT-qPCR analysis demonstrated consistent up-regulation of these lncRNAs in independent datasets. ROC curve analysis showed that two candidates were able to separate benign pleura and MPM with high sensitivity and specificity, and were associated with nodal metastases and survival following induction chemotherapy. These results suggest that lncRNAs have potential to serve as biomarkers in MPM. To identify mRNA and lncRNA biomarkers associated with malignant pleural mesothelioma (MPM), we performed gene expression array analysis on 4 MPM cell lines (H28, MM05, MSTO-211H, H226) compared to the immortalised mesothelial line (MeT-5A). All cell lines were profiled in duplicate. Synthesis of the labelled first strand cDNA was conducted using the Superscript Plus Direct cDNA labeling system with starting material of 10ug total RNA. The labeled dNTP mix was added to the reaction to generate labeled second strand cDNA. Following the hydrolysis reaction, single-stranded cDNA was purified using low elution volume spin cartridges included in the purification module. Samples were labelled using Alexa Fluor 555 dyes. Samples were then hybridised to NCode Long Noncoding RNA Microarrays. Slides were scanned using an Agilent Scanner. Genes differentially expressed between Met-5A and the MPM cell lines were identified on the basis of P-value and fold change.
2013-08-22 | E-GEOD-48174 | biostudies-arrayexpress
Project description:To identify gene expression biomarkers associated with asbestos-related lung adenocarcinoma, we analyzed primary tumour gene expression for a total of 36 primary lung adenocarcinomas on 22,323 element microarrays, comparing 12 patients with lung asbestos body counts above levels associated with urban dwelling (ARLC-AC: asbestos-related lung cancer-adenocarcinoma) with 24 patients with no asbestos bodies (NARLC-AC: non-asbestos related lung cancer-adenocarcinoma).
2010-05-28 | GSE20875 | GEO
Project description:Malignant mesothelioma (MpM) is an aggressive, fatal tumour, associated with asbestos exposure, for which there is no curative therapy and the mechanism of carcinogenesis is poorly understood. We use translational profiling to show that dysregulated post-transcriptional control makes a major contribution to aberrant cell growth in primary MpM cells, with elevated signalling through the mTOR axis activating mRNA translation initiation.
2020-11-10 | E-MTAB-8167 | biostudies-arrayexpress
Project description:To identify gene expression biomarkers associate with asbestos-related lung squamous cell carcinoma, we analyzed gene expression profiles for a total of 56 lung squamous cell carcinomas using 44K Illumina Gene Expression microarrays. Twenty-six cases had lung asbestos body counts above levels associated with urban dwelling (ARLC-SCC: asbestos-related lung cancer-squamous cell carcinoma) and 30 cases had no lung asbestos bodies (NARLC-SCC: non-asbestos related lung cancer- squamous cell carcinoma). Genes differentially expressed between ARLC-SCC and NARLC-SCC were identified on fold change and P-value, and then prioritised using gene ontology.
2012-01-30 | GSE23822 | GEO
Project description:To identify gene expression biomarkers associate with asbestos-related lung squamous cell carcinoma, we analyzed gene expression profiles for a total of 56 lung squamous cell carcinomas using 44K Illumina Gene Expression microarrays. Twenty-six cases had lung asbestos body counts above levels associated with urban dwelling (ARLC-SCC: asbestos-related lung cancer-squamous cell carcinoma) and 30 cases had no lung asbestos bodies (NARLC-SCC: non-asbestos related lung cancer- squamous cell carcinoma). Genes differentially expressed between ARLC-SCC and NARLC-SCC were identified on fold change and P-value, and then prioritised using gene ontology. Total RNA was obtained from fresh frozen lung tumour tissue and stratified by asbestos phenotype. Gene expression profiling was performed to identify differences in the gene profiles of asbestos-related and non-asbestos related lung squamous cell carcinomas.
2012-01-30 | E-GEOD-23822 | biostudies-arrayexpress
Project description:To identify gene expression biomarkers associated with asbestos-related lung adenocarcinoma, we analyzed primary tumour gene expression for a total of 36 primary lung adenocarcinomas on 22,323 element microarrays, comparing 12 patients with lung asbestos body counts above levels associated with urban dwelling (ARLC-AC: asbestos-related lung cancer-adenocarcinoma) with 24 patients with no asbestos bodies (NARLC-AC: non-asbestos related lung cancer-adenocarcinoma). To identify gene expression biomarkers associated with asbestos-related lung tumorigenicity, we performed gene expression array analysis on tumours of 36 patients with primary lung adenocarcinoma, comparing twelve patients with lung asbestos body counts above levels associated with urban dwelling (ARLC-AC: asbestos-related lung cancer-adenocarcinoma) with twenty-four patients with no asbestos bodies (NARLC-AC: non-asbestos related lung cancer-adenocarcinoma). Synthesis of the labelled first strand cDNA was conducted using Amersham CyScribe Post-Labelling kit with starting material of 20 ug of total RNA. The amino-allyl labeled dNTP mix was added to the reaction to generate amino-allyl labelled second strand cDNA. Following the hydrolysis reaction, single-stranded cDNA probes were purified using Amersham GFX columns. Dye coupling reactions were performed by mixing the cDNA samples with Amersham Cy3 (reference) or Cy5 (tumour) and incubating in the dark. The reactions were purified with Amersham GFX columns to remove the unincorporated/quenched dyes. After the purification samples were combined for hybridization, the labeled cDNAs were co-hybridized to 22K oligo microarrays. Slides were scanned on GMS418 confocal scanner (Agilent). Genes differentially expressed between ARLC-AC and NARLC-AC were identified on fold change and P-value, and then prioritised using gene ontology.
2010-05-28 | E-GEOD-20875 | biostudies-arrayexpress
Project description:We generated a blood-derived transcriptional signature that discriminates patients with lung cancer from non-affected smokers. When applied to blood samples from one of the largest prospective population-based cancer studies (the European Prospective Investigation into Cancer and Nutrition), this signature accurately predicted the occurrence of lung cancer in smokers within two years before the onset of clinical symptoms. Such a blood test could be used as a screening tool to enable early diagnosis of lung cancer at a curable stage. All samples were taken from smokers. EPIC cases were taken from the EPIC trial (a large prospective epidemiological trial in Europe, and are incident cases), Cosmos and BC cases are prevalent cases from a Cologne, Germany based epidemiological trial.
2010-02-28 | E-GEOD-12771 | biostudies-arrayexpress
Project description:Malignant pleural mesothelioma (MPM), which is associated with occupational asbestos exposure, is a deadly disease with no effective treatments due mainly to its high resistance to anti-cancer drugs. The molecular mechanisms responsible for its chemotherapeutic resistance are complicated and undefined. However, the presence of side population cells (SP cells) in tumors is a well-accepted explanation for their anti-cancer drug resistance. To identify SP cell-specific gene expression signature, microarray technique has been employed. Our data show differential gene expression profiles between SP and non-SP cells of H2714 mesothelioma cells. SP cells over-expressed genes associated with cancer stem cell (CSC) and drug resistance: DUSP6, SPRY2 and IL6, as well as multi-pathways, including the cancer stem cell-associated pathways Notch and c-Kit. Therefore, we believe that targeting CSC-specific genes and pathways in SP cells may hold the key to the discovery of effective treatments for reversing chemotherapeutic resistance to MPM treatment. 4 samples
2011-11-18 | E-GEOD-33734 | biostudies-arrayexpress
Project description:Malignant pleural mesothelioma (MPM) is an asbestos-related lethal malignancy refractory to conventional therapies. Since its symptoms are not specific, MPM can be easily confused with other chest diseases, especially metastatic lung adenocarcinomas (ADCA), and diagnosis is often established late when the disease is at an advanced stage. Classically, a reliable diagnosis requires histological analysis of multiple pleural biopsies. However, there is still no absolute marker for MPM. Thus, with the aim of identifying novel markers with higher specificity and sensitivity, gene expression profiling studies have been conducted using tumor specimens. Because of the cell heterogeneity of tumor samples, we decided to apply counterflow centrifugal elutriation to isolate cancer cells from pleural effusions, which are a common feature of MPM and ADCA. We profiled a total of 54 biological samples corresponding to triplicates of 13 MPM and 4 ADCA as well as the SV40-immortalized cell line MeT-5A. Our microarray results confirmed some of the existing markers which are currently used to distinguish MPM from ADCA by immunostaining of pleural biopsies and which have also been proposed for use in a PCR-based assay. Of particular interest, we also identified novel cellular markers (including predominantly COL3A1, OSAP, OCIAD2, XAGE1), which we validated by real time RT-PCR, and novel soluble markers, such as osteonectin and galectin-3, whose clinical utility as molecular targets remains to be determined. Keywords: cell type comparison three-condition experiment: ADCA vs MPM vs Met5A cells 13 MPM, 4 ADCA and Met5A were independantly grown and harvested 3 biological replicates per cell line, one replicate per array
2010-05-16 | E-GEOD-17310 | biostudies-arrayexpress