Background: Glioblastoma (GB) is one of the deadliest brain cancers with a bleak prognosis. It is characterized by highly proliferating tumor cells influenced by surrounding stroma, with a constant detectable communication between the tumor and its environmental components, which can be assessed in terms of specific proteins. Patients and Methods: To experimentally establish this cellular dialog, we undertook to evaluate plasma expression of three proteins： human telomerase reverse transcriptase (hTERT), chitinase-like protein (YKL-40), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in 66 individuals inclusive of thirty primary and two secondary GB patients and 34 age-matched controls, with reference to proliferation, angiogenesis, and extracellular matrix (ECM) degradation biomarkers. A fbllow-up at 3 months postsurgery fbr marker profile was done fbr GB. Results: Plasma levels of markers were higher in therapy-naive patients than in controls (P < 0.0001). In a 3-month fbllow-up, these levels were found to be higher in patients who survived fbr <4 months than nine patients who had lower values with better survival. A strong correlation existed between hTERT, YKL-40, and TIMP-1 levels； Cox regression analysis revealed higher levels of these circulating markers as poor prognostic indicators. The sensitivity of these markers increased to 96.9% in combination, thereby improving the accuracy of prognosis. Confbunders, i.e. age, site, and extent of resection, had no effect on the prognostication of these markers. Conclusion: These experimental blood-based data define the influence of angiogenesis and ECM remodeling on proliferation of GB relative to poor survival, using a panel ofbiomarkers. Evaluating the disease outcome noninvasively can pave the way fbr designing intervention strategy to control angiogenesis and ECM degradation and in turn tumor progression.
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