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基于蛋白质芯片的脑脊液研究揭示了低级别和高级别胶质瘤中不同的自身抗体特征。

A Protein Microarray-Based Investigation of Cerebrospinal Fluid Reveals Distinct Autoantibody Signature in Low and High-Grade Gliomas.

作者信息

Gahoi Nikita, Syed Parvez, Choudhary Saket, Epari Sridhar, Moiyadi Aliasgar, Varma Santosh G, Gandhi Mayuri N, Srivastava Sanjeeva

机构信息

Wadhwani Research Center for Biosciences and Bioengineering, Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India.

Centre for Research in Nanotechnology and Sciences, Indian Institute of Technology Bombay, Mumbai, India.

出版信息

Front Oncol. 2020 Dec 22;10:543947. doi: 10.3389/fonc.2020.543947. eCollection 2020.

Abstract

Gliomas are one of the most aggressive primary brain tumors arising from neural progenitor cells. Delayed diagnosis, invasive biopsy, and diagnostic challenges stems the need for specific, minimally-invasive, and early diagnostic biomarkers. Tumor-associated (TA) autoantibodies are measurable in the biofluids long before the onset of the symptoms, suggesting their role in early diagnosis and clinical management of the patients. In the current study, cerebrospinal fluid (CSF) samples from patients with low-grade glioma (LGG) and the (GBM) that characterizes advanced disease were compared with healthy control samples to identify putative TA autoantibodies, using protein microarrays. The CSF samples from LGGs (n = 10), GBM (n = 7) were compared with the control CSF samples (n = 6). Proteins showing significant antigenic response were cross-verified. Proteins NOL4 (a cancer-testis antigen) and KALRN showed an antigenic response in the CSF of GBM patients, whereas, UTP4 and CCDC28A showed an antigenic response in low grade gliomas when compared with the control samples. TA autoantibodies identified in this study from the CSF of the patients could supplement current screening modalities. Further validation of these TA autoantibodies on a larger clinical cohort could provide cues towards relevance of these proteins in early diagnosis of the disease.

摘要

胶质瘤是起源于神经祖细胞的最具侵袭性的原发性脑肿瘤之一。诊断延迟、侵入性活检以及诊断挑战引发了对特异性、微创和早期诊断生物标志物的需求。肿瘤相关(TA)自身抗体早在症状出现之前就能在生物流体中检测到,这表明它们在患者的早期诊断和临床管理中发挥着作用。在本研究中,使用蛋白质微阵列,将低级别胶质瘤(LGG)患者和代表晚期疾病的胶质母细胞瘤(GBM)患者的脑脊液(CSF)样本与健康对照样本进行比较,以鉴定潜在的TA自身抗体。将LGG患者(n = 10)、GBM患者(n = 7)的CSF样本与对照CSF样本(n = 6)进行比较。对显示出显著抗原反应的蛋白质进行交叉验证。蛋白质NOL4(一种癌胚抗原)和KALRN在GBM患者的脑脊液中显示出抗原反应,而与对照样本相比,UTP4和CCDC28A在低级别胶质瘤中显示出抗原反应。本研究从患者脑脊液中鉴定出的TA自身抗体可以补充当前的筛查方式。在更大的临床队列中对这些TA自身抗体进行进一步验证,可以为这些蛋白质在疾病早期诊断中的相关性提供线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8575/7784397/7846d4ed37d1/fonc-10-543947-g001.jpg

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