Engineering Mathematics, Ada Lovelace Building, Bristol BS8 1TW, UK.
Brain Tumour Research Centre, Bristol Medical School, Bristol BS2 8DZ, UK.
J R Soc Interface. 2022 Aug;19(193):20220180. doi: 10.1098/rsif.2022.0180. Epub 2022 Aug 3.
Brain tumours are the biggest cancer killer in those under 40 and reduce life expectancy more than any other cancer. Blood-based liquid biopsies may aid early diagnosis, prediction and prognosis for brain tumours. It remains unclear whether known blood-based biomarkers, such as glial fibrillary acidic protein (GFAP), have the required sensitivity and selectivity. We have developed a novel model which can be used to assess and compare blood-based liquid biopsies. We focused on GFAP, a putative biomarker for astrocytic tumours and glioblastoma multi-formes (GBMs). modelling was paired with experimental measurement of cell GFAP concentrations and used to predict the tumour volumes and identify key parameters which limit detection. The average GBM volumes of 449 patients at Leeds Teaching Hospitals NHS Trust were also measured and used as a benchmark. Our model predicts that the currently proposed GFAP threshold of 0.12 ng ml may not be suitable for early detection of GBMs, but that lower thresholds may be used. We found that the levels of GFAP in the blood are related to tumour characteristics, such as vasculature damage and rate of necrosis, which are biological markers of tumour aggressiveness. We also demonstrate how these models could be used to provide clinical insight.
脑肿瘤是 40 岁以下人群中最大的癌症杀手，比其他任何癌症都更能降低预期寿命。基于血液的液体活检可能有助于脑肿瘤的早期诊断、预测和预后。目前尚不清楚是否已知的基于血液的生物标志物，如神经胶质纤维酸性蛋白（GFAP），具有所需的灵敏度和选择性。我们已经开发了一种新的模型，可用于评估和比较基于血液的液体活检。我们专注于 GFAP，它是星形细胞瘤和胶质母细胞瘤多型（GBM）的潜在生物标志物。建模与细胞 GFAP 浓度的实验测量相结合，并用于预测肿瘤体积和确定限制检测的关键参数。还测量了利兹教学医院 NHS 信托基金会 449 名患者的平均 GBM 体积，并将其用作基准。我们的模型预测，目前提出的 0.12ng/ml 的 GFAP 阈值可能不适合 GBM 的早期检测，但可以使用较低的阈值。我们发现血液中 GFAP 的水平与肿瘤特征有关，例如血管损伤和坏死率，这些都是肿瘤侵袭性的生物标志物。我们还展示了如何使用这些模型提供临床见解。
