Evaluation of autoantibody signatures in meningioma patients using human proteome arrays
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Shabarni Gupta1,*, Shuvolina Mukherjee1,*, Parvez Syed1,2,*, Narendra Goud Pandala1, Saket Choudhary3,4, Vedita Anand Singh1, Namrata Singh1, Heng Zhu5, Sridhar Epari6, Santosh B. Noronha3, Aliasgar Moiyadi7 and Sanjeeva Srivastava1
1Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India
2Department of Biochemistry/Biotechnology, University of Turku, Turun yliopisto, Finland
3Department of Chemical Engineering, Indian Institute of Technology Bombay, Mumbai, India
4Molecular and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA
5Department of Pharmacology and Molecular Sciences/High-Throughput Biology Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
6Department of Pathology, Tata Memorial Centre, Mumbai, India
7Department of Neurosurgery, Tata Memorial Centre, Mumbai, India
*These authors have contributed equally to this work
Sanjeeva Srivastava, email: firstname.lastname@example.org
Keywords: meningioma, autoantibody, protein array, brain tumors, HuPort screening
Received: July 14, 2016 Accepted: March 11, 2017 Published: April 10, 2017
Meningiomas are one of the most common tumors of the Central nervous system (CNS). This study aims to identify the autoantibody biomarkers in meningiomas using high-density human proteome arrays (~17,000 full-length recombinant human proteins). Screening of sera from 15 unaffected healthy individuals, 10 individuals with meningioma grade I and 5 with meningioma grade II was performed. This comprehensive proteomics based investigation revealed the dysregulation of 489 and 104 proteins in grades I and II of meningioma, respectively, along with the enrichment of several signalling pathways, which might play a crucial role in the manifestation of the disease. Autoantibody targets like IGHG4, CRYM, EFCAB2, STAT6, HDAC7A and CCNB1 were significantly dysregulated across both the grades. Further, we compared this to the tissue proteome and gene expression profile from GEO database. Previously reported upregulated proteins from meningioma tissue-based proteomics obtained from high-resolution mass spectrometry demonstrated an aggravated autoimmune response, emphasizing the clinical relevance of these targets. Some of these targets like SELENBP1 were tested for their presence in tumor tissue using immunoblotting. In the light of highly invasive diagnostic modalities employed to diagnose CNS tumors like meningioma, these autoantibody markers offer a minimally invasive diagnostic platform which could be pursued further for clinical translation.
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