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 Glioblastoma multiforme (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.

Highlights

  • Gliomas are one of the most aggressive primary brain tumors characterized by high morbidity and mortality rates due to their localization, invasive, and heterogeneous nature [1]

  • The unsupervised clustering revealed that the Glioblastoma multiforme (GBM) samples clustered together but there was a significant overlap between lowgrade glioma (LGG) and Control samples (Supplementary Figure 1). These results revealed the presence of TA autoantibodies in the cerebrospinal fluid (CSF) of GBM samples is much higher as compared to low grade glioma samples

  • Gliomas are one of the most aggressive brain tumors and they are diagnosed at an advanced stage

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Summary

Introduction

Gliomas are one of the most aggressive primary brain tumors characterized by high morbidity and mortality rates due to their localization, invasive, and heterogeneous nature [1]. The 2016 WHO classification, grouped the diffused low-grade gliomas (WHO grade II) and intermediate-grade gliomas (WHO grade III) as low-grade gliomas (LGGs). These LGGs are further sub-divided based on the molecular markers like mutations in IDH, ATRX, TP53, and codeletion of 1p and 19q arms of chromosomes [3]. Pilocytic astrocytomas (WHO Grade I), the most common type of glioma in children, are molecularly distinct from adult gliomas. These are characterized by favorable prognosis, circumscribed growth and frequently carry BRAF gene mutations or fusion. Primary and secondary GBMs are histopathologically indistinguishable, they harbor different molecular alterations [4]

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