title: Long non coding RNAs (lncRNAs) are dysregulated in Malignant Pleural Mesothelioma (MPM).
abstract: Malignant Pleural Mesothelioma (MPM) is an aggressive cancer that is often diagnosed at an advanced stage and is characterized by a long latency period (20-40 years between initial exposure and diagnosis) and prior exposure to asbestos. Currently accurate diagnosis of MPM is difficult due to the lack of sensitive biomarkers and despite minor improvements in treatment, median survival rates do not exceed 12 months. Accumulating evidence suggests that aberrant expression of long non-coding RNAs (lncRNAs) play an important functional role in cancer biology. LncRNAs are a class of recently discovered non-protein coding RNAs >200 nucleotides in length with a role in regulating transcription. Here we used NCode long noncoding microarrays to identify differentially expressed lncRNAs potentially involved in MPM pathogenesis. High priority candidate lncRNAs were selected on the basis of statistical (P<0.05) and biological significance (>3-fold difference). Expression levels of 9 candidate lncRNAs were technically validated using RT-qPCR, and biologically validated in three independent test sets: (1) 57 archived MPM tissues obtained from extrapleural pneumonectomy patients, (2) 15 cryopreserved MPM and 3 benign pleura, and (3) an extended panel of 10 MPM cell lines. RT-qPCR analysis demonstrated consistent up-regulation of these lncRNAs in independent datasets. ROC curve analysis showed that two candidates were able to separate benign pleura and MPM with high sensitivity and specificity, and were associated with nodal metastases and survival following induction chemotherapy. These results suggest that lncRNAs have potential to serve as biomarkers in MPM.
authors: Asbestos Diseases Research Institute, The University of Sydney, Concord New South Wales, Australia.
authors: Casey M
authors: CM
authors: Wright
authors: Michaela B
authors: MB
authors: Kirschner
authors: Yuen Yee
authors: YY
authors: Cheng
authors: Kenneth J
authors: KJ
authors: O'Byrne
authors: Steven G
authors: SG
authors: Gray
authors: Karin
authors: K
authors: Schelch
authors: Mir Alireza
authors: MA
authors: Hoda
authors: Sonja
authors: S
authors: Klebe
authors: Brian
authors: B
authors: McCaughan
authors: Nico
authors: N
authors: van Zandwijk
authors: Glen
authors: G
authors: Reid
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008654:Mesothelioma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010997:Pleural Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D062085:RNA, Long Noncoding / Q000235:genetics*; D012372:ROC Curve; D016019:Survival Analysis; D015854:Up-Regulation
chemical_list: D062085:RNA, Long Noncoding
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