Can a novel combination panel of five systemic biomarkers define the prognosis and provide a target for therapy in high grade glioma?

Abstract

Abstract Purpose High-grade gliomas (HGG) comprise WHO grades 3 and 4 and despite multimodal therapy, the overall-survival(OS) has not improved much. In this study, the markers representing four-partakers of the tumor-microenvironment (TME) were identified that can help to monitor disease progression, namely Interleukin6 (IL6, inflammation), inducible nitrous-synthase (iNOS, hypoxia), vascular-endothelial growth-receptor(VEGF) and Endothelin1(ET1) (angiogenesis) and intercellular-adhesion molecule1(ICAM1, extracellular-matrix). Their systemic expression in HGG was quantified noninvasively. Methods 76 therapy-naive patients with HGG and 30 controls were considered in this study. Serum/plasma was analyzed for systemic expressions of IL-6, iNOS, VEGF, ET1, and ICAM1 qualitatively by dot-immune-assay and quantitatively by ELISA. Results Markers IL-6, iNOS, VEGF, ET1, and ICAM1 were screened by DIA, their expression was significantly higher in grade-4 compared to grade-3 and controls. Quantification of circulating levels of the markers presented a similar result. The biomarkers were observed to negatively correlate with OS (p < 0.0001). Cox-regression analysis yielded all chosen biomarkers as good prognostic indicators; independent of confounders. The biomarker panel achieved higher sensitivity than single markers, to define survival on applying combination statistics. The association of iNOS, VEGF, ET1, and ICAM1 with IL6 was significant, hinting of a crosstalk and an inflammation driven expression of other partakers of TME. Conclusion This is a first-ever experimental study of a marker-panel that could distinguish between histopathological grades, and also delineate differential survival using liquid-biopsy, suggesting that these markers can serve as a target for personalized-therapy. The panel of biomarkers of IL-6, iNOS, VEGF, ET1, and ICAM1 holds promise for prognostication in HGG.