Intracranial Aneurysm Biomarker Candidates Identified by a Proteome-Wide Study

Tanavi Sharma, Keshava K. Datta, Munish Kumar, Gourav Dey, Aafaque Ahmad Khan, Kiran Kumar Mangalaparthi, Poonam Saharan, Shobia Chinnapparaj, Ashish Aggarwal, Navneet Singla, Sujata Ghosh, Amit Rawat, Sivashanmugam Dhandapani, Pravin Salunke, Rajesh Chhabra, Dalbir Singh, Aastha Takkar, Sunil K. Gupta, Thottethodi Subrahmanya Keshava Prasad, Harsha GowdaKanchan K. Mukherjee, Akhilesh Pandey, Hemant Bhagat

Research output: Contribution to journalArticle

Abstract

The scientific basis of intracranial aneurysm (IA) formation, its rupture and further development of cerebral vasospasm is incompletely understood. Aberrant protein expression may drive structural alterations of vasculature found in IA. Deciphering the molecular mechanisms underlying these events will lead to identification of early detection biomarkers and in turn, improved treatment outcomes. To unravel differential protein expression in three clinical subgroups of IA patients: (1) unruptured aneurysm, (2) ruptured aneurysm without vasospasm, (3) ruptured aneurysm who developed vasospasm, we performed untargeted quantitative proteomic analysis of aneurysm tissue and serum samples from three subgroups of IA patients and control subjects. Candidate molecules were then validated in a larger cohort of patients using enzyme-linked immunosorbent assay. A total of 937 and 294 proteins were identified from aneurysm tissue and serum samples, respectively. Several proteins that are known to maintain structural integrity of vasculature were found to be dysregulated in the context of aneurysm. ORM1, a glycoprotein, was significantly upregulated in both tissue and serum samples of unruptured aneurysm patients. We employed a larger cohort of subjects (n = 26) and validated ORM1 as a potential biomarker for screening of unruptured aneurysms. Samples from ruptured aneurysms with vasospasm showed significant upregulation of MMP9, a protease, compared with ruptured aneurysms without vasospasm. We validated MMP9 as a potential biomarker for vasospasm in a larger cohort (n = 52). This study reports the first global proteomic analysis of the entire clinical spectrum of IA. Furthermore, this study suggests ORM1 and MMP9 as potential biomarkers for unruptured aneurysm and cerebral vasospasm, respectively.

Original languageEnglish (US)
Pages (from-to)483-492
Number of pages10
JournalOMICS A Journal of Integrative Biology
Volume24
Issue number8
DOIs
StatePublished - Aug 1 2020

Keywords

  • biomarker
  • cerebral vasospasm
  • intracranial aneurysm
  • mass spectrometry
  • proteomics
  • subarachnoid hemorrhage

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics

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  • Cite this

    Sharma, T., Datta, K. K., Kumar, M., Dey, G., Khan, A. A., Mangalaparthi, K. K., Saharan, P., Chinnapparaj, S., Aggarwal, A., Singla, N., Ghosh, S., Rawat, A., Dhandapani, S., Salunke, P., Chhabra, R., Singh, D., Takkar, A., Gupta, S. K., Prasad, T. S. K., ... Bhagat, H. (2020). Intracranial Aneurysm Biomarker Candidates Identified by a Proteome-Wide Study. OMICS A Journal of Integrative Biology, 24(8), 483-492. https://doi.org/10.1089/omi.2020.0057