Malignant Pleural Mesothelioma (MM) is an asbestos-related malignancy which is detected at an advanced stage when curative options are not feasible. Sensitive and specific early detection biomarkers for MM such as SMRP and Osteopontin (OPN) await validation, and prognostic biomarkers which can segregate patients at highest risk for progression/death do not exist. The North American Mesothelioma Consortium (NAMC) joins investigators at centers which are known for specific expertise in MM and prognostic/early detection investigations in order to develop a multifaceted approach for the rapid discovery and eventual validation of such markers. Biomarker discovery will involve three separate but related platforms: genomic expression, microRNA expression, and serum anti-glycan antibodies (AGA). Preliminary data using in silico analysis of MM expression profiling has revealed a promising metagene-type prognostic model. Analysis of 132 MM fresh frozen tumors reveals that a single microRNA, 29c*, can segregate MM patients into groups with short and long times to progression, and groups with short and long survival. Finally, using a novel glycan array capable of measuring serum AGAs to over 200 glycans, patients with asbestos exposure without MM can be segregated from those with MM (AUC 0.863) with 4 AGAs, and a profile of 6 autoantibodies can predict progression and survival outcomes for MM patients. All three of the discovery platforms for the NAMC will be linked by a common reference set of normal mesothelium and tumor samples with matching sera in order to relate promising markers from each platform to pathways involved with the other platforms using a systems biology approach. Using these common materials, the NAMC will further discover/validate (1) the metagene prognostic profile, (2) the ability of 29c* to define MM prognosis, (3) other microRNAs for early detection of MM, and (4) the repertoire of AGA for the early detection/prognostication of MM. In addition to these studies, early detection and validation studies of plasma OPN will also be performed. All of these studies can be immediately performed since the NAMC has access through the NYU Archives to over 287 MM/107 normal mesothelium fresh frozen tissues, 339 MM sera, and 797 asbestos-exposed sera from three different geographic locations.
Asbestos-exposed individuals are at risk for the development of MM. Only early stage patients benefit from multimodality therapy. To date there have been no successful screening efforts for these cohorts. Discovery of serum/tissue based markers pre-dating MM development and/or guiding clinicians regarding patient outcomes could have profound, worldwide economic and health related implications for MM management.
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