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Overexpressed genes in malignant pleural mesothelioma: implications in clinical management.

ABSTRACT: Malignant pleural mesothelioma (MPM) is a very aggressive cancer poorly responsive to current therapies. MPM patients have a very poor prognosis with a median survival of less than one year from the onset of symptoms. The biomarkers proposed so far do not lead to a sufficiently early diagnosis for a radical treatment of the disease. Thus, the finding of novel diagnostic and prognostic biomarkers and therapeutic targets is needed. Gene overexpression has been frequently associated with a malignant phenotype in several cancer types; therefore the identification of overexpressed genes may lead to the detection of novel prognostic or diagnostic marker and to the development of novel therapeutic approaches, based on their inhibition. In the last years, several overexpressed genes have been identified in MPM through gene expression profiling techniques: among them it has been found a group of 51 genes that resulted overexpressed in more than one independent study, revealing their consistency among studies. This article reviews the clinical implications of confirmed overexpressed genes in MPM described so far in literature.

SUBMITTER: Barone E

PROVIDER: S-EPMC5830549 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Overexpressed genes in malignant pleural mesothelioma: implications in clinical management.

Barone Elisa E Gemignani Federica F Landi Stefano S

Journal of thoracic disease 20180101 Suppl 2

Malignant pleural mesothelioma (MPM) is a very aggressive cancer poorly responsive to current therapies. MPM patients have a very poor prognosis with a median survival of less than one year from the onset of symptoms. The biomarkers proposed so far do not lead to a sufficiently early diagnosis for a radical treatment of the disease. Thus, the finding of novel diagnostic and prognostic biomarkers and therapeutic targets is needed. Gene overexpression has been frequently associated with a malignan ...[more]

PMID: 29507807

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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 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.

Dataset Information

Overexpressed genes in malignant pleural mesothelioma: implications in clinical management.

Publications

Overexpressed genes in malignant pleural mesothelioma: implications in clinical management.

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