Dataset Information

Survival and pleurodesis response markers in malignant pleural effusion – The PROMISE study

ABSTRACT: Background: Malignant pleural effusion (MPE) is a common condition that indicates advanced malignancy, incurability and short life expectancy. While MPE incidence is increasing worldwide, prognostic biomarkers to plan treatment and to understand the underlying mechanisms of disease progression remain unidentified. Objective: To discover, validate, and prospectively assess biomarkers of survival and pleurodesis response in MPE. To combine clinical, radiologic, and pleural fluid biologic parameters in order to build a score that forecasts survival. Conclusions: The PROMISE score is the first prospectively validated prognostic model for MPE that combines biological and clinical parameters to accurately estimate 3-month mortality.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung

SUBMITTER: Philip Charles

LAB HEAD: Ioannis Psallidas

PROVIDER: PXD008682 | Pride | 2018-07-17

REPOSITORIES: pride

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			Action	DRS
	QE0469b_20151106_IoannisP_002.raw	Raw
	QE0469b_20151106_IoannisP_003_151109180149.raw	Raw
	QE0469b_20151106_IoannisP_004.raw	Raw
	QE0469b_20151106_IoannisP_005_151118031840.raw	Raw
	QE0469b_20151106_IoannisP_006.raw	Raw

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Publications

Development and validation of response markers to predict survival and pleurodesis success in patients with malignant pleural effusion (PROMISE): a multicohort analysis.

Psallidas Ioannis I Kanellakis Nikolaos I NI Gerry Stephen S Thézénas Marie Laëtitia ML Charles Philip D PD Samsonova Anastasia A Schiller Herbert B HB Fischer Roman R Asciak Rachelle R Hallifax Robert J RJ Mercer Rachel R Dobson Melissa M Dong Tao T Pavord Ian D ID Collins Gary S GS Kessler Benedikt M BM Pass Harvey I HI Maskell Nick N Stathopoulos Georgios T GT Rahman Najib M NM

The Lancet. Oncology 20180613 7

<h4>Background</h4>The prevalence of malignant pleural effusion is increasing worldwide, but prognostic biomarkers to plan treatment and to understand the underlying mechanisms of disease progression remain unidentified. The PROMISE study was designed with the objectives to discover, validate, and prospectively assess biomarkers of survival and pleurodesis response in malignant pleural effusion and build a score that predicts survival.<h4>Methods</h4>In this multicohort study, we used five separ ...[more]

PMID: 29908990

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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.