Genomic and Transcriptomic Analysis of Pleural Mesothelioma (MPM) Samples Reveal Crucial Insights for Preclinical Testing
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PROVIDER: PRJEB61319 | ENA |
REPOSITORIES: ENA
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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: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:Diagnosis of malignant pleural mesothelioma (MPM) is difficult, the most common differential diagnosis being benign pleural diseases and metastatic adenocarcinomas. In order to identify novel markers able to improve diagnostic accuracy, we performed a genome-wide gene expression analysis on tumor cells lines established from pleural effusions (13 MPM and 4 lung adenocarcinoma). Our microarray analysis led to the identification of genes encoding novel cellular and soluble markers whose expression was validated by RT-qPCR. Immunohistochemical staining of tumor biopsies with anti-type-III collagen antibodies were positive in mesothelioma cells but not in adenocarcinoma cells. Using ELISA, we showed that the C-C motif chemokine 2 (CCL2) concentration was significantly higher in pleural effusions from patients with mesothelioma (n = 61) than in subjects with adenocarcinoma (n = 25) or with benign pleural effusions (n = 15): median (interquartile range) = 2.99 ng/mL (1.76-6.01) versus 0.99 ng/mL (0.51-1.83) and 1.47 ng/mL (0.80-1.56), respectively, P < 0.0001. Conversely, the galectin-3 concentration was lower in mesothelioma: 11.50 ng/mL (6.73-23.53) versus 24.74 ng/mL (20.42-70.35) and 17.64 ng/mL (14.81-24.68), respectively, P < 0.0001. The AUC for CCL2 were 0.8030 and 0.7716 for differentiating mesothelioma from adenocarcinoma or benign effusions, respectively. Similarly, the AUC obtained for galectin-3 were 0.7980 and 0.6923, respectively. In conclusion, type-III collagen, CCL2 and galectin-3 are promising new diagnostic markers for mesothelioma.
2009-07-25 | GSE17310 | GEO
Project description:To identify regions that display DNA copy number alterations in malignant pleural mesothelioma (MPM), we carried out array comparative genomic hybridization (CGH) analysis with 14 MPM cell lines. Regions of genomic aberrations observed in >20% of individuals were 9p21.3, 13q12.11, 16p13, and 22q12.2 of losses. The most frequent alteration was 9p21.3, which include the p16INK4/p14ARF. The loss of 22q12.2 regions include the NF2 was observed in 3 out of 14 cell lines. In 3 cell lines, loss of 13q12.11 region which contains Large Tumor Suppressor, homolog 2 (LATS2) was detected. Human malignant pleural mesothelioma cell lines were profiled on Agilent 244K aCGH arrays according to manufacturer’s instructions. Pooled normal human genomic DNA was used as the reference.
2010-06-15 | E-GEOD-22237 | biostudies-arrayexpress
Project description:Diagnosis of malignant pleural mesothelioma (MPM) is a challenging task because of its overlap with other neoplasms or even reactive conditions. Recently, DNA methylation analysis proved to be an effective tool for tumor diagnosis. We thus set out to test this approach for MPM diagnosis. A discovery (n=33) and an independent validation cohort (n=46) of MPM samples were subjected to array-based DNA methylation analyses and their DNA methylation patterns were compared to a representative set of both malignant and benign diagnostic mimics. By both unsupervised hierarchical clustering and t-distributed stochastic neighbor embedding analysis, MPM samples of the discovery cohort exhibited a distinct DNA methylation profile, different from that of other neoplastic and reactive mimics.
2021-03-20 | GSE164269 | GEO
Project description:To identify regions that display DNA copy number alterations in malignant pleural mesothelioma (MPM), we carried out array comparative genomic hybridization (CGH) analysis with 14 MPM cell lines. Regions of genomic aberrations observed in >20% of individuals were 9p21.3, 13q12.11, 16p13, and 22q12.2 of losses. The most frequent alteration was 9p21.3, which include the p16INK4/p14ARF. The loss of 22q12.2 regions include the NF2 was observed in 3 out of 14 cell lines. In 3 cell lines, loss of 13q12.11 region which contains Large Tumor Suppressor, homolog 2 (LATS2) was detected.
2010-06-15 | GSE22237 | GEO
Project description:We characterized tumor and immune microenvironment (TiME) of malignant pleural mesothelioma (MPM) using immunoproteomic approach to comprehensively understand the landscape to affect prognosis and possibly to predict response to immunotherapy. Time-of-Flight Mass Cytometry (CyTOF) was performed on the tumors of 12 MPM patients. We comprehensively analyzed TiME by developing intuitive models for visualizing single-cell data with statistical inference and performed unsupervised clustering of cell frequency. A clinically relevant protein signature through mass spectrometry and mRNA transcriptome array was tested for its ability to reflect prognosis in three independent cohorts (n=330) and to predict response to immune checkpoint inhibitor therapy in publicly available data and in 10 patients of MPM treated with anti-PD1 therapy. A systematic understanding of antitumor immunity by immunoproteomic characterization of TiME envisions significant progress in developing rational immunotherapeutic strategies in MPM.
2018-04-05 | GSE99070 | GEO
Project description:Malignant pleural mesothelioma (MPM) is a deadly pleural malignancy with over 90% mortality within five years and a median survival of approximately 7 months without treatment. The current first-line chemotherapy, a combination of pemetrexed and cisplatin, modestly extends survival, with the addition of bevacizumab offering a further 2-month benefit. Radiation therapy, while not effective as a primary treatment due to the extensive field required, plays a role in multimodal approaches or as localized therapy. The diversity in patient outcomes and responses to treatments indicates significant tumor heterogeneity in MPM, underscoring the need for therapies that consider this variability and target the molecular specifics of individual MPM cases. Tumor heterogeneity is observed at both intertumor and intratumor levels, encompassing tumor cells and their microenvironments. Molecular profiling studies have further highlighted this heterogeneity, complicating the identification of a unique biomarker for MPM.
2024-01-04 | GSE247203 | GEO
Project description:Malignant pleural mesothelioma (MPM) is an aggressive malignancy with poor prognosis. Unlike many other cancers, MPM is mostly characterized by inactivation of tumor suppressor genes. Its highly malignant nature in absence of tumor driving oncogene mutations indicates an extrinsic supply of stimulating signals by cells of the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are an abundant cell type of the TME and have been shown to drive the progression of several cancer types. The aim of the current study was to isolate and characterize patient-derived mesothelioma-associated fibroblasts (Meso-CAFs), and evaluate their impact on MPM cells.
2022-12-31 | E-MTAB-12179 | 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