Discovery and validation of astrocytoma biomarkers using microdissected tissue specimens coupled with targeted and mass spectrometry-based proteomic studies

ANYL 318

Tong Guo, tguo@umd.edu1, Weijie Wang, weijie.wang@calibrant.com2, Cheng S. Lee, clee1@umd.edu1, Zhengping Zhuang, Zhuangp@ninds.nih.gov3, Robert Weil4, and Brian M. Balgley, brian.balgley@calibrant.com2. (1) Department of Chemistry & Biochemistry, University of Maryland, College Park, Building 091, College Park, MD 20742, (2) Calibrant Biosystems, 910 Clopper Road, Suite 220N, Gaithersburg, MD 20878, (3) National Institute of Neurological Disorders and Stroke, Surgical Neurology Branch, Bldg 10, Rm 5D37, Bethesda, MD 20892, (4) Brain Tumor and Neuro-Oncology Center, Cleveland Clinic Foundation, Mail Code: ND40, 9500 Euclid Avenue, Cleveland, OH 44195
Mass spectrometry-based proteomic studies have emerged as a powerful tool for biomarker discovery using body fluids, cells, and tissues. However, biomarker discovery efforts have been challenged by the complexity, dynamic range, and quality of proteomes in clinical specimens. Due to the low levels of tumor-associated proteins in serum, a targeted approach, involving the use of clinically well-defined fresh frozen tissues coupled with tissue microdissection, novel proteome technologies and bioinformatics, has been employed to identify and validate unique biomarkers for diagnostic and prognostic applications related to astrocytoma staging including distinction among grade II astrocytoma, grade III anaplastic astrocytoma, and grade IV glioblastoma multiforme. These quantitative and comparative proteome studies generate candidate lists for validation using liquid chromatography-single reaction monitoring, and tissue microarray immunohistochemistry.