Gupta Shabarni, Mukherjee Shuvolina, Syed Parvez, Pandala Narendra Goud, Choudhary Saket, Singh Vedita Anand, Singh Namrata, Zhu Heng, Epari Sridhar, Noronha Santosh B, Moiyadi Aliasgar, Srivastava Sanjeeva
Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India.
Department of Biochemistry/Biotechnology, University of Turku, Turun yliopisto, Finland.
Oncotarget. 2017 Apr 10;8(35):58443-58456. doi: 10.18632/oncotarget.16997. eCollection 2017 Aug 29.
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.
脑膜瘤是中枢神经系统(CNS)最常见的肿瘤之一。本研究旨在使用高密度人类蛋白质组芯片(约17,000种全长重组人类蛋白质)鉴定脑膜瘤中的自身抗体生物标志物。对15名未受影响的健康个体、10名I级脑膜瘤患者和5名II级脑膜瘤患者的血清进行了筛查。这项基于蛋白质组学的全面研究分别揭示了I级和II级脑膜瘤中489种和104种蛋白质的失调,以及几种信号通路的富集,这可能在疾病表现中起关键作用。IGHG4、CRYM、EFCAB2、STAT6、HDAC7A和CCNB1等自身抗体靶点在两个级别中均显著失调。此外,我们将此与来自GEO数据库的组织蛋白质组和基因表达谱进行了比较。先前报道的基于脑膜瘤组织蛋白质组学(通过高分辨率质谱获得)中上调的蛋白质显示出加剧的自身免疫反应,强调了这些靶点的临床相关性。其中一些靶点,如SELENBP1,使用免疫印迹法检测其在肿瘤组织中的存在情况。鉴于用于诊断脑膜瘤等中枢神经系统肿瘤的侵入性很强的诊断方法,这些自身抗体标志物提供了一个微创诊断平台,可进一步进行临床转化研究。