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基质中血小板衍生生长因子受体β(PDGFR-β)的表达是高级别浆液性卵巢癌患者的一个预后因素,但它是否也能预测抗血管生成治疗的反应?

Stromal PDGFR-beta expression is a prognostic factor in high-grade serous ovarian cancer patients but is it also predictive for response to antiangiogenic treatment?

作者信息

Volk Annabelle, von Bülow Charlotte, Stern Aysche, Simon Ronald, Burandt Eike, Sauter Guido, Schmalfeldt Barbara, Oliveira-Ferrer Leticia

机构信息

Department of Gynecology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.

Department of Internal Medicine, Southwest Healthcare, Temecula, USA.

出版信息

J Cancer Res Clin Oncol. 2025 Jan 24;151(2):44. doi: 10.1007/s00432-025-06090-4.

Abstract

OBJECTIVE

In advanced ovarian cancer, the majority of patients receive anti-angiogenic treatment with bevacizumab. However, its use is often associated with severe side effects, and not all patients benefit from the therapy. Currently, there are no reliable biomarkers to predict response to treatment. Given their role as key regulators of angiogenesis, platelet-derived growth factor receptor-beta (PDGFR-beta) and vascular endothelial growth factor receptor-2 (VEGFR-2) are promising candidates for predictive biomarkers. This study evaluates their potential.

METHODS

PDGFR-beta and VEGFR-2 expression was evaluated using immunohistochemistry in a tissue microarray assay including 391 ovarian tissue samples. Correlation analyses with clinical and histopathological parameters were performed in a homogeneous cohort of 199 high grade serous ovarian cancer samples (HGSOC).

RESULTS

In HGSOC, strong stromal PDGFR-beta expression was associated with significantly shorter overall survival compared to weak/moderate expression. The impact of stromal PDGFR-beta expression on patient survival was however not restricted to the subgroup of patients receiving therapy with bevacizumab, and therefore cannot be considered as a predictive factor. For VEGFR-2, no or weak protein expression was found in the majority of the tumor samples. Survival analyses showed a more favorable prognosis with no or weak VEGFR-2 expression.

CONCLUSIONS

High stromal expression levels of PDGFR-beta correlate with shorter overall survival in HGSOC. Thus, stromal PDGFR-beta might serve as a prognostic biomarker. No predictive effect in response to bevacizumab therapy could be attributed.

摘要

目的

在晚期卵巢癌中,大多数患者接受贝伐单抗抗血管生成治疗。然而,其使用常伴有严重副作用,且并非所有患者都能从该治疗中获益。目前,尚无可靠的生物标志物来预测治疗反应。鉴于血小板衍生生长因子受体-β(PDGFR-β)和血管内皮生长因子受体-2(VEGFR-2)作为血管生成的关键调节因子的作用,它们有望成为预测性生物标志物。本研究评估了它们的潜力。

方法

在包含391个卵巢组织样本的组织微阵列分析中,使用免疫组织化学评估PDGFR-β和VEGFR-2的表达。在199个高级别浆液性卵巢癌样本(HGSOC)的同质队列中,进行了与临床和组织病理学参数的相关性分析。

结果

在HGSOC中,与弱/中度表达相比,强基质PDGFR-β表达与显著缩短的总生存期相关。然而,基质PDGFR-β表达对患者生存的影响并不局限于接受贝伐单抗治疗的患者亚组,因此不能被视为预测因素。对于VEGFR-2,在大多数肿瘤样本中未发现或仅有弱蛋白表达。生存分析显示,VEGFR-2无表达或弱表达时预后更有利。

结论

HGSOC中PDGFR-β的高基质表达水平与较短的总生存期相关。因此,基质PDGFR-β可能作为一种预后生物标志物。未发现其对贝伐单抗治疗反应有预测作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00f4/11774546/cd7dccc7e250/432_2025_6090_Fig1_HTML.jpg

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