Tau蛋白和IV型胶原蛋白的降解片段作为接受纳武单抗和贝伐单抗治疗的复发性胶质母细胞瘤患者的血清生物标志物

Degradation fragments of Tau and type IV collagen as serum biomarkers in patients with recurrent glioblastoma treated with nivolumab and bevacizumab.

作者信息

Jensen Christina, Maarup Simone, Poulsen Hans Skovgaard, Hasselbalch Benedikte, Karsdal Morten, Svane Inge Marie, Lassen Ulrik, Willumsen Nicholas

机构信息

Nordic Bioscience A/S, Herlev, Denmark.

The DCCC Brain Tumor Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

出版信息

Clin Transl Oncol. 2025 Jun;27(6):2761-2767. doi: 10.1007/s12094-024-03775-z. Epub 2024 Nov 5.

DOI:10.1007/s12094-024-03775-z

PMID:39499486

Abstract

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.

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仍有未满足的需求。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降解的VI型胶原蛋白（C4G）和基质金属蛋白酶（C4M），以及ADAM10降解的Tau（Tau-A）。

方法

将接受纳武单抗和贝伐单抗治疗的复发性GBM患者（n = 39）（NCT03890952）治疗前和治疗期间血清样本中的生物标志物水平与健康水平（n = 22）进行比较，并与总生存期（OS）结果（中位数切点）相关联。通过混合效应分析研究生物标志物的纵向变化。

结果

患者的Tau-A（p < 0.0001）和C4G（p = 0.005）升高，但C4M未升高（p = 0.106）。高Tau-A和C4G与改善的OS相关（Tau-A：HR = 0.41，95%CI = 0.20 - 0.86，C4G：HR = 0.47，95%CI = 0.24 - 0.94）。只有C4G随治疗增加（p = 0.024 - 0.005）。