高级别胶质瘤 (HGG) 包括 WHO 3 级和 4 级，总体生存率 (OS) 较差，在过去十年中并未得到改善。在此，鉴定了代表肿瘤微环境（TME）四个组成部分的标记物，以定义它们在 TME 中的相关表达并预测 HGG 的预后，即白细胞介素 6（IL6，炎症）、诱导型一氧化氮合酶（iNOS）、热休克蛋白。 70（HSP70，缺氧）、血管内皮生长受体（VEGF）、内皮素 1（ET1）（血管生成）、基质金属蛋白酶 14（MMP14）和细胞间粘附分子 1（ICAM1，细胞外基质）。建立用于 HGG 精确预测的非侵入性生物标志物组。对 86 名未接受过治疗的 HGG 患者和 45 名对照者进行了确定的小组分析。通过斑点免疫测定 (DIA) 筛选细胞外/分泌生物标志物的系统表达，通过 ELISA 进行定量，并通过免疫细胞化学 (ICC) 进行验证。 iNOS、HSP70、IL-6、VEGF、ET1、MMP14 和 ICAM1 的表达与分级呈正相关。通过 ELISA 和 ICC 对标记物的循环水平进行定量，得出了类似的结果。观察到生物标志物与 OS 呈负相关 (p<<0.0001)。 Cox 回归分析得出的所有生物标志物都是良好的预后指标，并且独立于混杂因素。在应用组合统计数据时，生物标志物组在定义生存方面比单一标志物具有更高的灵敏度。所有七种生物标志物的内部关联都很显着，暗示 TME 成分与缺氧驱动的全身炎症之间存在串扰，从而上调其他成分的表达。这是首次对标记物组进行实验研究，该标记物组可以区分组织病理学分级，并使用液体活检描绘差异生存，表明缺氧标记物可以成为个性化治疗的基石。 iNOS、HSP70、IL-6、VEGF、ET1、MMP14 和 ICAM1 生物标志物组有望在 HGG 中进行预测。© 2024。作者获得 Springer Science Business Media, LLC 的独家许可，该公司是施普林格自然。

High-grade gliomas (HGG) comprising WHO grades 3 and 4 have a poor overall survival (OS) that has not improved in the past decade. Herein, markers representing four components of the tumor microenvironment (TME) were identified to define their linked expression in TME and predict the prognosis in HGG, namely, interleukin6 (IL6, inflammation), inducible nitric oxide synthase(iNOS), heat shock protein-70 (HSP70, hypoxia), vascular endothelial growth receptor (VEGF), and endothelin1 (ET1) (angiogenesis) and matrix metalloprotease-14 (MMP14) and intercellular adhesion molecule1 (ICAM1, extracellular matrix). To establish a non-invasive panel of biomarkers for precise prognostication in HGG. Eighty-six therapy-naive HGG patients with 45 controls were analyzed for the defined panel. Systemic expression of extracellular/secretory biomarkers was screened dot-immune assay (DIA), quantified by ELISA, and validated by immunocytochemistry (ICC). Expression of iNOS, HSP70, IL-6, VEGF, ET1, MMP14, and ICAM1 was found to be positively associated with grade. Quantification of circulating levels of the markers by ELISA and ICC presented a similar result. The biomarkers were observed to negatively correlate with OS (p < 0.0001). Cox-regression analysis yielded all biomarkers as good prognostic indicators and independent of confounders. On applying combination statistics, the biomarker panel achieved higher sensitivity than single markers to define survival. The intra-association of all seven biomarkers was significant, hinting of a cross-talk between the TME components and a hypoxia driven systemic inflammation upregulating the expression of other components. This is a first ever experimental study of a marker panel that can distinguish between histopathological grades and also delineate differential survival using liquid biopsy, suggesting that markers of hypoxia can be a cornerstone for personalized therapy. The panel of biomarkers of iNOS, HSP70, IL-6, VEGF, ET1, MMP14, and ICAM1 holds promise for prognostication in HGG.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.