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整合素α2β1是原发性卵巢癌的一种预后和预测生物标志物。

Integrin α2β1 Represents a Prognostic and Predictive Biomarker in Primary Ovarian Cancer.

作者信息

Dötzer Katharina, Schlüter Friederike, Koch Franz Edler von, Brambs Christine E, Anthuber Sabine, Frangini Sergio, Czogalla Bastian, Burges Alexander, Werner Jens, Mahner Sven, Mayer Barbara

机构信息

Department of General, Visceral and Transplant Surgery, University Hospital, Ludwig-Maximilians-University Munich, Marchioninistraße 15, 81377 Munich, Germany.

Gynecology and Obstetrics Clinic, Klinikum Dritter Orden, Menzinger Straße 44, 80638 Munich, Germany.

出版信息

Biomedicines. 2021 Mar 12;9(3):289. doi: 10.3390/biomedicines9030289.

Abstract

Currently, the same first-line chemotherapy is administered to almost all patients suffering from primary ovarian cancer. The high recurrence rate emphasizes the need for precise drug treatment in primary ovarian cancer. Being crucial in ovarian cancer progression and chemotherapeutic resistance, integrins became promising therapeutic targets. To evaluate its prognostic and predictive value, in the present study, the expression of integrin α2β1 was analyzed immunohistochemically and correlated with the survival data and other therapy-relevant biomarkers. The significant correlation of a high α2β1-expression with the estrogen receptor alpha (ERα; = 0.035) and epithelial growth factor receptor (EGFR; = 0.027) was observed. In addition, high α2β1-expression was significantly associated with a low number of tumor-infiltrating immune cells (CD3 intratumoral, = 0.017; CD3 stromal, = 0.035; PD-1 intratumoral, = 0.002; PD-1 stromal, = 0.049) and the lack of PD-L1 expression ( = 0.005). In Kaplan-Meier survival analysis, patients with a high expression of integrin α2β1 revealed a significant shorter progression-free survival (PFS, = 0.035) and platinum-free interval (PFI, = 0.034). In the multivariate Cox regression analysis, integrin α2β1 was confirmed as an independent prognostic factor for both PFS ( = 0.021) and PFI ( = 0.020). Dual expression of integrin α2β1 and the hepatocyte growth factor receptor (HGFR; PFS/PFI, = 0.004) and CD44v6 (PFS, = 0.000; PFI, = 0.001; overall survival [OS], = 0.025) impaired survival. Integrin α2β1 was established as a prognostic and predictive marker in primary ovarian cancer with the potential to stratify patients for chemotherapy and immunotherapy, and to design new targeted treatment strategies.

摘要

目前,几乎所有原发性卵巢癌患者都接受相同的一线化疗。高复发率凸显了原发性卵巢癌精准药物治疗的必要性。整合素在卵巢癌进展和化疗耐药中起关键作用,成为了有前景的治疗靶点。为评估其预后和预测价值,在本研究中,采用免疫组织化学方法分析了整合素α2β1的表达,并将其与生存数据及其他与治疗相关的生物标志物进行关联。观察到α2β1高表达与雌激素受体α(ERα;P = 0.035)和表皮生长因子受体(EGFR;P = 0.027)显著相关。此外,α2β1高表达与肿瘤浸润免疫细胞数量少(肿瘤内CD3,P = 0.017;基质中CD3,P = 0.035;肿瘤内PD-1,P = 0.002;基质中PD-1,P = 0.049)及PD-L1表达缺失(P = 0.005)显著相关。在Kaplan-Meier生存分析中,整合素α2β1高表达的患者无进展生存期(PFS,P = 0.035)和无铂间期(PFI,P = 0.034)显著缩短。在多变量Cox回归分析中,整合素α2β1被确认为PFS(P = 0.021)和PFI(P = 0.020)的独立预后因素。整合素α2β1与肝细胞生长因子受体(HGFR;PFS/PFI,P = 0.004)和CD44v6(PFS,P = 0.000;PFI,P = 0.001;总生存期[OS],P = 0.025)的双重表达损害生存。整合素α2β1被确立为原发性卵巢癌的预后和预测标志物,具有对患者进行化疗和免疫治疗分层以及设计新的靶向治疗策略的潜力。

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