Human Mesothelioma MicroRNA Study Part 1
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE40345 | GEO | 2013/10/01
SECONDARY ACCESSION(S): PRJNA173644
REPOSITORIES: GEO
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Project description:MicroRNA expression profiles of malignant pleural mesothelioma (MPM) specimens were analyzed to identify novel microRNA that are potentially involved in the oncogenic transformation of human pleural cells. In addition to several novel MPM-associated microRNAs, we observed that the expression level of microRNA-1 was significantly lower in tumors as compared to normal pleural specimens. Subsequently, pre-mir of microRNA-1 was introduced into MPM cell lines to overexpress this microRNA. Phenotypic changes of these altered cells were assayed. The cellular proliferation rate was significantly inhibited after overexpression of microRNA-1. Early and late apoptosis were measured by Annexin V and TUNEL assays, respectively. Taken together, these data suggested that overexpression of microRNA-1 induced apoptosis in these MPM cell lines, acting as a tumor suppressor. We confirmed our observations by assessing in the transduced MPM cells cell cycle-related genes, pro-apoptotic and anti-apoptotic genes, which all showed coordinated, significant changes characteristic of the apoptotic phenotype. Thus, further investigation and validation of our microRNA database of MPM may elucidate previously unrecognized molecular pathways and/ or mechanisms by identifying novel microRNAs that are involved in malignant transformation. Our study has now found microRNA-1 to be one of these MPM-associated microRNAs, with potential pathogenic and therapeutic significance. MicroRNA microarray transcriptional profiling studies of 25 MPM primary tumors as well 6 normal pleural samples from an unmatched patient cohort as normal comparators were performed.
2013-10-01 | E-GEOD-40345 | biostudies-arrayexpress
Project description:BACKGROUND: Malignant pleural mesothelioma (MPM) is difficult to distinguish from reactive mesothelial proliferations (RMPs). MicroRNAs (miRNAs) are small non-coding RNA-strands (~22 nucleotides) that post-transcriptionally regulate gene-expression. Studies have shown that miRNAs are potential diagnostic markers in other cancers; however, it is uncertain whether miRNAs are useful biomarkers for differentiating MPM from RMP. OBJECTIVE: To identify differentially expressed microRNAs which can aid in the diagnostics of MPM. METHODS: We screened with a quantitative RT-PCR (RT-qPCR)-based platform the expression of 742 miRNAs in formalin-fixed paraffin-embedded (FFPE) preoperative diagnostic biopsies, surgically resected MPM-specimens previously treated with chemotherapy, and corresponding non-neoplastic pleura (NNP) from 5 patients. RESULTS: By comparing the change in microRNA expression in patient-matched tissue samples, we identify 14 miRNAs which exhibit statistically significant deregulation between sample groups. CONCLUSION: Based on this initial screening of miRNA expression, we have identified 14 miRNAs which are potential diagnostic biomarkers and may aid in diffferentiating RMP from MPM. qPCR microRNA expression profiling. MicroRNA expression in surgical tissue samples and presurgery diagnostic biopsies of malignant pleural mesotheliomas was compared to corresponding patient-matched non-neoplastic pleura. Patient-matched diagnostic biopsies from still chemotherapy-naïve patients were included to test for chemotherapy-induced changes in microRNA expression.
2014-01-25 | E-GEOD-54394 | biostudies-arrayexpress
Project description:BACKGROUND: Malignant pleural mesothelioma (MPM) is difficult to distinguish from reactive mesothelial proliferations (RMPs). MicroRNAs (miRNAs) are small non-coding RNA-strands (~22 nucleotides) that post-transcriptionally regulate gene-expression. Studies have shown that miRNAs are potential diagnostic markers in other cancers; however, it is uncertain whether miRNAs are useful biomarkers for differentiating MPM from RMP. OBJECTIVE: To identify differentially expressed microRNAs which can aid in the diagnostics of MPM. METHODS: We screened with a quantitative RT-PCR (RT-qPCR)-based platform the expression of 742 miRNAs in formalin-fixed paraffin-embedded (FFPE) preoperative diagnostic biopsies, surgically resected MPM-specimens previously treated with chemotherapy, and corresponding non-neoplastic pleura (NNP) from 5 patients. RESULTS: By comparing the change in microRNA expression in patient-matched tissue samples, we identify 14 miRNAs which exhibit statistically significant deregulation between sample groups. CONCLUSION: Based on this initial screening of miRNA expression, we have identified 14 miRNAs which are potential diagnostic biomarkers and may aid in diffferentiating RMP from MPM.
2014-01-25 | GSE54394 | GEO
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
Project description:Malignant pleural mesothelioma (MPM) is a highly lethal, poorly understood neoplasm that is typically associated with asbestos exposure. We performed transcriptional profiling using high-density oligonucleotide microarrays containing approximately 22,000 genes to elucidate potential molecular and pathobiological pathways in MPM using discarded human MPM tumor specimens (n=40), normal lung specimens (n=4), normal pleura specimens (n=5), and MPM and SV40-immortalized mesothelial cell lines (n=5). In global expression analysis using unsupervised clustering techniques, we found two potential subclasses of mesothelioma which correlate loosely with tumor histology. We also identified sets of genes with expression levels that distinguish between multiple tumor subclasses, normal and tumor tissues, and tumors with different morphologies. Microarray gene expression data were confirmed using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and protein analysis for three novel candidate oncogenes (NME2, CRI1, and PDGFC) and one candidate tumor suppressor (GSN). Finally, we used bioinformatics tools (i.e. software) to create and explore complex physiological pathways that may be relevant in mesothelioma tumorigenesis, pathobiology, or both. Tissues and cell lines profiled using microarrays. Discarded MPM surgical specimens (n=40), normal pleura specimens (n=5), and normal lung specimens (n=4) were freshly collected (and snap frozen) from patients who underwent surgery at Bostonâs Brigham and Womenâs Hospital (BWH) between October 1998 and August 2000. All of these patients underwent extrapleural pneumonectomy with heated intra-pleural cisplatin chemotherapy delivered after the specimens were removed. All normal specimens were obtained from patients who were never diagnosed with MPM. Two human MPM cell lines (MS589 and MS428) were kindly provided by Jonathan A. Fletcher, M.D., Department of Pathology, BWH. The JMN1B MPM cell line19,20 has been described previously. The SV40-immortalized, non-tumorigenic mesothelial cell line (Met-5A)21 and the MPM cell line MSTO-211H22 were purchased from the American Type Culture Collection. Normal tissues were obtained from additional consented patients undergoing treatment for diseases other than MPM. All MPM samples used in these studies contained relatively pure tumor (greater than 50% tumor cells per high power field examined in a section adjacent to the tissue used). The microscopic slides from the patientsâ resection specimens were reviewed by one of the authors (J.G.), and the diagnosis and histologic subclassification of MPM confirmed in all cases. Linked clinical and pathological data were obtained for all patients who contributed tumor specimens. Specimens and data were rendered anonymous to protect patient confidentiality. Studies utilizing human tissues were approved by and conducted in accordance with the policies of the Institutional Review Board at BWH. SUBMITTER_CITATION: Gordon, G. J., Rockwell, G. N., Jensen, R. V., Rheinwald, J. G., Glickman, J.N., Aronson, J. P., Pottorf, B. J., Nitz, M. D., Richards, W. G., Sugarbaker, D. J., and Bueno, R. Identification of novel candidate oncogenes and tumor suppressors in malignant pleural mesothelioma using large-scale transcriptional profiling. American Journal of Pathology, 166: 1827-1840, 2005.
2007-08-25 | E-GEOD-2549 | biostudies-arrayexpress
Project description:Malignant pleural mesothelioma (MPM) is a highly lethal, poorly understood neoplasm that is typically associated with asbestos exposure. We performed transcriptional profiling using high-density oligonucleotide microarrays containing approximately 22,000 genes to elucidate potential molecular and pathobiological pathways in MPM using discarded human MPM tumor specimens (n=40), normal lung specimens (n=4), normal pleura specimens (n=5), and MPM and SV40-immortalized mesothelial cell lines (n=5). In global expression analysis using unsupervised clustering techniques, we found two potential subclasses of mesothelioma which correlate loosely with tumor histology. We also identified sets of genes with expression levels that distinguish between multiple tumor subclasses, normal and tumor tissues, and tumors with different morphologies. Microarray gene expression data were confirmed using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and protein analysis for three novel candidate oncogenes (NME2, CRI1, and PDGFC) and one candidate tumor suppressor (GSN). Finally, we used bioinformatics tools (i.e. software) to create and explore complex physiological pathways that may be relevant in mesothelioma tumorigenesis, pathobiology, or both. Tissues and cell lines profiled using microarrays. Discarded MPM surgical specimens (n=40), normal pleura specimens (n=5), and normal lung specimens (n=4) were freshly collected (and snap frozen) from patients who underwent surgery at Boston's Brigham and Women's Hospital (BWH) between October 1998 and August 2000. All of these patients underwent extrapleural pneumonectomy with heated intra-pleural cisplatin chemotherapy delivered after the specimens were removed. All normal specimens were obtained from patients who were never diagnosed with MPM. Two human MPM cell lines (MS589 and MS428) were kindly provided by Jonathan A. Fletcher, M.D., Department of Pathology, BWH. The JMN1B MPM cell line19,20 has been described previously. The SV40-immortalized, non-tumorigenic mesothelial cell line (Met-5A)21 and the MPM cell line MSTO-211H22 were purchased from the American Type Culture Collection. Normal tissues were obtained from additional consented patients undergoing treatment for diseases other than MPM. All MPM samples used in these studies contained relatively pure tumor (greater than 50% tumor cells per high power field examined in a section adjacent to the tissue used). The microscopic slides from the patients' resection specimens were reviewed by one of the authors (J.G.), and the diagnosis and histologic subclassification of MPM confirmed in all cases. Linked clinical and pathological data were obtained for all patients who contributed tumor specimens. Specimens and data were rendered anonymous to protect patient confidentiality. Studies utilizing human tissues were approved by and conducted in accordance with the policies of the Institutional Review Board at BWH.
2005-06-01 | GSE2549 | GEO
Project description:Transcriptome analysis following knock down of LSD1 in ACC-MESO-1 cells. Malignant pleural mesothelioma (MPM) is a highly aggressive tumor that has a low overall survival; however, no significant treatment advances have been made in the past 15 years. In this study we investigated whether targeting lysine-specific demethylase 1 (LSD1/KDM1), a histone-modifying enzyme responsible for demethylating histone H3 lysine 4 and lysine 9, could represent a novel therapeutic strategy for patients with MPM. We found that suppressing LSD1 induces an epithelial phenotype in sarcomatoid MPM cells, while attenuating the mesenchymal phenotype sensitized MPM cells to cisplatin-induced apoptosis through the FAK pathway. To investigate the potential mechanisms underlying FAK pathway activation, we performed transcriptome analysis using two different shRNA constructs against the LSD1.
2021-08-10 | GSE181735 | GEO
Project description:MiRNA screening was performed to identify differentially expressed miRNAs in a series of 14 formalin fixed paraffin-embedded (FFPE) malignant pleural mesothelioma (MPM) samples representative of the epithelioid, biphasic and sarcomatoid histotypes in comparison with normal mesothelium. MiRNA expression in FFPE MPM and normal mesothelial specimens was analyzed through the miRCURY™ LNA™ Array microRNA Profiling Service (Exiqon). RNA samples were subjected to quality control and, subsequently, 450 ng were labelled with the Hy3™ fluorescent label with the miRCURY™ LNA™ Array power labelling kit. A common reference, against which each individual sample could be tested to assay biological variations among the specimens, was constituted by pooling equal amounts of RNA from each tumor and control and labelled with Hy5™. The Hy3™-labelled samples and the Hy5™-labelled reference RNA sample were mixed pair-wise and hybridized to the miRCURY™ LNA™ array version 11.0 (208200-A Exiqon) according to the manufacturer instructions.
2020-09-16 | E-MTAB-8790 | biostudies-arrayexpress
Project description:For establishing a live-cell biobank of Malignant Pleural Mesothelioma (MPM) samples, cultures of two MPM patients were compared to the original tumor tissue using Affymetrix OncoScan Microarrays for genome-wide CNV and LOH detection.
2018-01-18 | GSE109305 | GEO
Project description:Treatment of malignant pleural mesothelioma (MPM) cells with anti-CD26Ab inhibits tumor progression and phase I clinical application of anti-CD26Ab resulted in prolonged disease stabilization in patients with advanced/refractory MPM. In order to elucidate the molecular mechanism of anti-CD26Ab to inhibit MPM progression, microarray analysis was performed on anti-CD26Ab treated MPM cells.
2018-08-01 | GSE100848 | GEO