Sequential Binary Gene-Ratio Tests Define a Novel Molecular Diagnostic Strategy for Malignant Pleural Mesothelioma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE42977 | GEO | 2013/05/01
SECONDARY ACCESSION(S): PRJNA183995
REPOSITORIES: GEO
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Project description:The gene-expression ratio technique was used to design a molecular signature to diagnose MPM from among other potentially confounding diagnoses and differentiate the epithelioid from the sarcomatoid histological subtype of MPM. Microarray analysis was performed on 113 specimens including MPMs and a spectrum of tumors and benign tissues comprising the differential diagnosis of MPM. A sequential combination of binary gene-expression ratio tests was developed to discriminate MPM from other thoracic malignancies . This method was compared to other bioinformatic tools and this signature was validated in an independent set of 170 samples. Functional enrichment analysis was performed to identify differentially expressed probes.
2013-05-01 | E-GEOD-42977 | biostudies-arrayexpress
Project description:We applied a spatially resolved, high-dimensional transcriptomic approach to study MPM morpho-logical evolution. 139 regions across 8 biphasic MPMs (B-MPMs) were profiled using the GeoMx™Digital Spatial Profiler and Cancer Transcriptome Atlas to compare epithelioid and sarcomatoid components transcriptional profile and reconstruct the positional context of transcriptional activities and the spatial topology of MPM cells interactions.
2023-12-07 | E-MTAB-13043 | biostudies-arrayexpress
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:Objective: Immune checkpoint therapy (ICT) has significantly impacted malignant pleural mesothelioma (MPM) treatment. Despite some promising results from combination therapies, nearly half of MPM patients do not benefit, underscoring the urgent need for reliable predictive biomarkers. This study assesses the prognostic value of serum soluble mesothelin-related peptide (SMRP) and PD-L1 levels in MPM patients receiving ICT. Results: Seventy-seven patients (62%) were treated with either anti-PD-(L)1 monotherapy, while the remaining 38% were given combination ICT. Higher pre-ICT SMRP levels were notably observed in epithelioid versus non-epithelioid MPM. Serum PD-L1 levels did not show significant differences between the groups. Univariable analysis identified durable clinical benefits, development of immune-related adverse events, and SMRP levels as significantly associated with OS. Multivariable analysis confirmed SMRP as an independent prognostic factor, with lower levels (≤1.35 nmol/L) correlating with improved OS (median survival: 23 months vs. 13 months). This finding was further validated in the prospective ICT clinical trial cohort. Conclusions: SMRP emerges as a promising serum biomarker for predicting survival in MPM patients treated with ICT, warranting further prospective investigation.
2024-08-19 | GSE274983 | 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: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:PurposeTo develop a standardized approach for molecular diagnostics, we used the gene expression ratio bioinformatic technique to design a molecular signature to diagnose malignant pleural mesothelioma (MPM) from among other potentially confounding diagnoses and differentiate the epithelioid from the sarcomatoid histologic subtype of MPM. In addition, we searched for pathways relevant in MPM in comparison with other related cancers to identify unique molecular features in MPM.Experimental designWe conducted microarray analysis on 113 specimens including MPMs and a spectrum of tumors and benign tissues comprising the differential diagnosis of MPM. We generated a sequential combination of binary gene expression ratio tests able to discriminate MPM from other thoracic malignancies. We compared this method with other bioinformatic tools and validated this signature in an independent set of 170 samples. Functional enrichment analysis was conducted to identify differentially expressed probes.ResultsA sequential combination of gene expression ratio tests was the best molecular approach to distinguish MPM from all the other samples. Bioinformatic and molecular validations showed that the sequential gene ratio tests were able to identify the MPM samples with high sensitivity and specificity. In addition, the gene ratio technique was able to differentiate the epithelioid from the sarcomatoid type of MPM. Novel genes and pathways specifically activated in MPM were identified.ConclusionsNew clinically relevant molecular tests have been generated using a small number of genes to accurately distinguish MPMs from other thoracic samples, supporting our hypothesis that the gene expression ratio approach could be a useful tool in the differential diagnosis of cancers.
| S-EPMC3644001 | biostudies-literature
Project description:The gene-expression ratio technique was used to design a molecular signature to diagnose MPM from among other potentially confounding diagnoses and differentiate the epithelioid from the sarcomatoid histological subtype of MPM. Microarray analysis was performed on 113 specimens including MPMs and a spectrum of tumors and benign tissues comprising the differential diagnosis of MPM. A sequential combination of binary gene-expression ratio tests was developed to discriminate MPM from other thoracic malignancies . This method was compared to other bioinformatic tools and this signature was validated in an independent set of 170 samples. Functional enrichment analysis was performed to identify differentially expressed probes.
| S-ECPF-GEOD-42977 | biostudies-other
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:Malignant mesothelioma (MM) is an asbestos-related malignancy. Discrimination between MM and reactive mesothelial hyperplasia (RM) is often difficult. MM cells have a broad histological spectrum, and consist mainly of epithelioid, sarcomatoid, and biphasic cell types. The prognosis of MM is generally poor, but better prognosis has been reported with the epithelioid type of MM than the non-epithelioid type. We applied a genome-wide analysis to the identification of new markers that may aid in differentiating the epithelioid type of MM from other histological types and from RM cells.
2014-11-22 | GSE52788 | GEO