Unravelling the role of Exosomes as early non-invasive predictors of disease state in Glioblastoma

Abstract

Abstract Background Gliobastoma are the malignant grade 4 astrocytic tumours, which accounts for the major cause of recurrence or death amongst all the brain tumours. The biology to pathophysiology of the tumour being complex, the search for specific differential markers always remains the need of an hour for disease treatment and monitoring. Liquid biopsy approach has open newer avenues to study and regulate the disease in a non-invasive manner. The study focuses to find the some newer regulatory genes by a liquid biopsy approach. Methodology: Meta-analysis was carried for the already published datasets pertaining to Glioblastoma by Gene Spring software. The top listed genes were validated in tissue and exosomes of the patients. Sixty tissue samples and 30 blood (serum) samples were collected from the glioma patients. Expression analysis was carried out by quantitative real time PCR. The results were statistically analyzed using SPSS 16.0 and PRISM software. Results Meta-analysis fetched the top 9 highly upregulated genes inclusive of CD44, VEGFA, TGFβ1, THBS1, SERPINE1, TAGLN2, ATF3, FOSL2, FABP5. Amongst these genes, CD44, VEGFA, TGFβ1, THBS1 and SERPINE1 showed the significant differential expression between low grade and high grade gliomas tissue samples. These five significant genes when analysed in the exosomal RNA, prominent differential expression was observed. Conclusion The study conclusively shows that CD44, VEGFA, TGFβ1, THBS1 and SERPINE1 could collectively work as hub genes to differentiate high grade gliomas from low grade tumours. Moreover, blood serum could serve as a better liquid biopsy marker in case of high infiltrating GBM tumours.