Christina Jensen, Simone Maarup, Hans Skovgaard Poulsen, Benedikte Hasselbalch, Morten Karsdal, Inge Marie Svane, Ulrik Lassen, Nicholas Willumsen
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引用次数: 0
摘要
目的：胶质母细胞瘤（GBM）患者对新的治疗方案和生物标志物的需求尚未得到满足。在此，我们研究了三种非侵入性生物标志物：分别由颗粒酶 B（C4G）和基质金属蛋白酶（C4M）降解的 VI 型胶原，以及 ADAM10 降解的 Tau（Tau-A）：将接受尼伐单抗和贝伐单抗（NCT03890952）治疗的复发性GBM患者（39人）治疗前和治疗中血清样本中的生物标志物水平与健康人（22人）的水平进行比较，并将其与总生存期（OS）结果（中位数切点）相关联。通过混合效应分析研究了生物标志物的纵向变化：结果：Tau-A（p复发性 GBM 患者血清中的 Tau-A 和 C4G 升高，是 OS 的预后指标。如果得到验证，这些生物标记物可应用于临床试验。
Degradation fragments of Tau and type IV collagen as serum biomarkers in patients with recurrent glioblastoma treated with nivolumab and bevacizumab.
Purpose: There is an unmet need for new treatment options and biomarkers for patients with glioblastoma (GBM). Here we investigated three non-invasive biomarkers: type VI collagen degraded by granzyme B (C4G) and matrix metalloproteases (C4M), respectively, and ADAM10-degraded Tau (Tau-A).
Methods: Biomarker levels in pre- and on-treatment serum samples from patients with recurrent GBM (n = 39) treated with nivolumab and bevacizumab (NCT03890952) were compared to healthy levels (n = 22) and associated with overall survival (OS) outcome (median cutpoint). Longitudinal changes in biomarkers were investigated by a Mixed-effects analysis.
Results: Tau-A (p < 0.0001) and C4G (p = 0.005), but not C4M (p = 0.106), were increased in patients. High Tau-A and C4G associated with improved OS (Tau-A: HR = 0.41, 95%CI = 0.20-0.86, C4G: HR = 0.47, 95%CI = 0.24-0.94). Only C4G increased with treatment (p = 0.024-0.005).
Conclusions: Tau-A and C4G are elevated in serum from patients with recurrent GBM and prognostic for OS. If validated, these biomarkers could be applied to clinical trials.
期刊介绍：
Clinical and Translational Oncology is an international journal devoted to fostering interaction between experimental and clinical oncology. It covers all aspects of research on cancer, from the more basic discoveries dealing with both cell and molecular biology of tumour cells, to the most advanced clinical assays of conventional and new drugs. In addition, the journal has a strong commitment to facilitating the transfer of knowledge from the basic laboratory to the clinical practice, with the publication of educational series devoted to closing the gap between molecular and clinical oncologists. Molecular biology of tumours, identification of new targets for cancer therapy, and new technologies for research and treatment of cancer are the major themes covered by the educational series. Full research articles on a broad spectrum of subjects, including the molecular and cellular bases of disease, aetiology, pathophysiology, pathology, epidemiology, clinical features, and the diagnosis, prognosis and treatment of cancer, will be considered for publication.
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