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抗 DLL4 纳米抗体预测胃癌患者 DLL4 作为预后生物标志物的研究

The Prediction of DLL4 as a Prognostic Biomarker in Patients with Gastric Cancer Using Anti-DLL4 Nanobody.

机构信息

Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.

Department of Radiology, Faculty of Para-Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.

出版信息

J Gastrointest Cancer. 2024 Sep;55(3):1380-1387. doi: 10.1007/s12029-024-01093-9. Epub 2024 Jul 24.

Abstract

BACKGROUND

Angiogenesis and cancer metastasis depend on the DLL4/Notch signaling pathway. A new approach to treating angiogenesis could inhibit or block this pathway. In the present study, we investigated DLL4 expression as a biomarker capable of predicting survival outcomes in gastric cancer patients using a novel anti-DLL4 Nanobody.

PATIENTS AND METHODS

By using a recently developed anti-DLL4 Nanobody, the expression of DLL4 was evaluated in tissue samples from 135 gastric cancer patients. It was evaluated whether DLL4 expression is related to clinicopathological factors, overall survival (OS), and recurrence-free survival (RFS).

RESULTS

Sixty-five (48%) gastric cancer patients had a positive expression of DLL4 within the tumor tissue. Based on both the univariate and multivariate regression analyses, the expression of DLL4 was strongly associated with RFS (HR, 1.94; p = 0.008) and OS (HR, 2.06; p = 0.004). Moreover, the survival analysis demonstrated that DLL4 expression was a significant independent factor of unfavorable OS (HR, 2.7; p = 0.01) and RFS (HR, 2.3; p = 0.02) in gastric cancer patients.

CONCLUSION

DLL4 expression in gastric cancer patients may predict poor prognosis and survival. Furthermore, the current data demonstrate the potential of Nanobody for detecting DLL4, and it may lead to develop novel therapies and diagnostics for tumors.

摘要

背景

血管生成和癌症转移依赖于 DLL4/Notch 信号通路。一种新的治疗血管生成的方法可以抑制或阻断这条通路。在本研究中,我们使用一种新的抗 DLL4 Nanobody 作为生物标志物,研究了 DLL4 表达与胃癌患者生存结果的关系。

患者与方法

使用最近开发的抗 DLL4 Nanobody,评估了 135 例胃癌患者组织样本中 DLL4 的表达情况。评估 DLL4 表达与临床病理因素、总生存期(OS)和无复发生存期(RFS)的关系。

结果

65 例(48%)胃癌患者肿瘤组织中 DLL4 表达阳性。单因素和多因素回归分析均表明,DLL4 表达与 RFS(HR,1.94;p=0.008)和 OS(HR,2.06;p=0.004)密切相关。此外,生存分析表明,DLL4 表达是胃癌患者 OS(HR,2.7;p=0.01)和 RFS(HR,2.3;p=0.02)不良的独立显著因素。

结论

胃癌患者 DLL4 表达可能预示预后不良和生存不良。此外,目前的数据表明 Nanobody 检测 DLL4 具有潜力,并可能为肿瘤的治疗和诊断带来新的途径。

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