The road-map for establishment of a prognostic molecular marker panel in glioma using liquid biopsy: current status and future directions.

Gliomas are primary intracranial tumors with defined molecular markers available for precise diagnosis. The prognosis of glioma is bleak as there is an overlook of the dynamic crosstalk between tumor cells and components of the microenvironment. Herein, different phases of gliomagenesis are presented with reference to the role and involvement of secreted proteomic markers at various stages of tumor initiation and development. The secreted markers of inflammatory response, namely interleukin-6, tumor necrosis factor-α, interferon-ϒ, and kynurenine, proliferation markers human telomerase reverse transcriptase and microtubule-associated-protein-Tau, and stemness marker human-mobility-group-AThook-1 are involved in glial tumor initiation and growth. Further, hypoxia and angiogenic factors, heat-shock-protein-70, endothelial-growth-factor-receptor-1 and vascular endothelial growth factor play a major role in promoting vascularization and tumor volume expansion. Eventually, molecules such as matrix-metalloprotease-7 and intercellular adhesion molecule-1 contribute to the degradation and remodeling of the extracellular matrix, ultimately leading to glioma progression. Our study delineates the roadmap to develop and evaluate a non-invasive panel of secreted biomarkers using liquid biopsy for precisely evaluating disease progression, to accomplish a clinical translation.