血管内皮生长因子 (VEGF) -A、-C 和 VE-钙粘蛋白作为早期乳腺癌患者的潜在生物标志物。
Vascular endothelial growth factor (VEGF) -A, -C and VE-cadherin as potential biomarkers in early breast cancer patients.
发表日期:2023 Nov 05
作者:
Jelena Milovanović, Tijana Vujasinović, Nataša Todorović-Raković, John Greenman, Jelena Hranisavljević, Marko Radulovic
来源:
BIOMEDICINE & PHARMACOTHERAPY
摘要:
血管内皮生长因子(VEGF)-A和-C作为多功能分子和生长因子,而VE-钙粘蛋白(cadherin 5、CDH5)是内皮连接蛋白。评估瘤内VEGF-A、-C和CDH5之间的关系原发性早期乳腺癌患者的水平和临床结果。该研究包括 69 名淋巴结阴性 (N0) 乳腺癌患者,所有患者均未接受过任何会影响病程的激素或化疗全身治疗。中位随访期为 144 个月。通过RT-qPCR测定瘤内VEGF-A、-C和CDH5的mRNA水平。通过 Cox 比例风险回归、Kaplan-Meier 分析以及基于最小绝对收缩和选择算子 (LASSO) logit 回归的多变量方法来评估预后表现。使用以结果为导向的截止点分类方法将患者分为低亚组和高亚组。在测量的 mRNA 中,仅 CDH5 mRNA (t = -2.17; p = 0.04) 和 VEGF-C mRNA (t = - 2.41;p = 0.03)分别显示有远处转移的患者亚组和没有复发的患者亚组的值之间存在显着差异。这些 t 检验结果与 Cox 回归一致,其中 CDH5 mRNA 达到最显着的风险比(HR=2.07;p = 0.05),其次是 VEGF-C mRNA(HR=1.59;p = 0.005)。 HR 值高于 1.0 表明 CDH5 或 VEGF-C mRNA 高水平与不良临床结果的风险较高相关。 CDH5high 亚组的远处复发率为 26%,CDH5low 亚组的远处复发率为 3%(Kaplan-Meier 分析)。 VEGF-Chigh 亚组的远处复发率为 23%,VEGF-Clow 亚组的远处复发率为 0%。 VEGF-C mRNA 的独立预后价值通过 LASSO 回归得到证实。肿瘤内 VEGF-A 水平与原发性早期乳腺癌患者的疾病结局无关,而 CDH5 或 VEGF-C 水平升高则预示着较高的预后。远处转移的风险。版权所有 © 2023 Elsevier GmbH。版权所有。
Vascular endothelial growth factor (VEGF) -A and -C act as multifunctional molecules and growth factors, while VE-cadherin (cadherin 5, CDH5) is the endothelial junction protein.To assess the relationship between intratumoral VEGF -A, -C and CDH5 levels and clinical outcome, in primary, early-stage, breast cancer patients.The study included 69 node-negative (N0) breast cancer patients, all of whom had not received any prior hormonal or chemotherapeutic systemic therapy that would affect the course of disease. The median follow-up period was 144 months. Intratumoral mRNA levels of VEGF -A, -C and CDH5 were determined by RT-qPCR. Prognostic performance was evaluated by Cox proportional hazards regression, Kaplan-Meier analysis, as well as by the multivariable approach based on the least absolute shrinkage and selection operator (LASSO) logit regression. Classification of patients into the low and high subgroups was performed using the outcome-oriented cut-off point categorization approach.Of the measured mRNAs, only CDH5 mRNA (t = -2.17; p = 0.04) and VEGF-C mRNA (t = -2.41; p = 0.03) showed significant differences between values in patient subgroups with distant metastasis and those without recurrences, respectively. These t-test results were in agreement with the Cox regression by which CDH5 mRNA reached the most pronounced hazard ratio (HR=2.07; p = 0.05), followed by VEGF-C mRNA (HR=1.59; p = 0.005). HR values above 1.0 indicate that high levels of either CDH5 or VEGF-C mRNAs associated with a higher risk of poor clinical outcome. Distant recurrence incidence was 26% for the CDH5high and 3% for the CDH5low subgroup (Kaplan-Meier analysis). Distant recurrence incidence was 23% for the VEGF-Chigh and 0% for VEGF-Clow subgroup. The independent prognostic value of VEGF-C mRNA was confirmed by LASSO regression.Intratumoral VEGF-A levels did not associate with disease outcome in primary, early-stage, breast cancer patients, whilst raised levels of either CDH5 or VEGF-C prognosticated a high risk of distant metastasis.Copyright © 2023 Elsevier GmbH. All rights reserved.