Fry Simon A, Robertson Claire E, Swann Ruth, Dwek Miriam V
Faculty of Science and Technology, Department of Molecular and Applied Biosciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK.
Faculty of Science and Technology, Department of Human and Health Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK.
Br J Cancer. 2016 Apr 26;114(9):1019-26. doi: 10.1038/bjc.2016.66. Epub 2016 Mar 24.
A glycoproteomic study has previously shown cadherin-5 (CDH5) to be a serological marker of metastatic breast cancer when both protein levels and glycosylation status were assessed. In this study we aimed to further validate the utility of CDH5 as a biomarker for breast cancer progression.
A nested case-control study of serum samples from breast cancer patients, of which n=52 had developed a distant metastatic recurrence within 5 years post-diagnosis and n=60 had remained recurrence-free. ELISAs were used to quantify patient serum CDH5 levels and assess glycosylation by Helix pomatia agglutinin (HPA) binding. Clinicopathological, treatment and lifestyle factors associated with metastasis and elevated biomarker levels were identified.
Elevated CDH5 levels (P=0.028) and ratios of CDH5:HPA binding (P=0.007) distinguished patients with metastatic disease from those that remained metastasis-free. Multivariate analysis showed that the association between CDH5:HPA ratio and the formation of distant metastases was driven by patients with oestrogen receptor (ER+) positive cancer with vascular invasion (VI+).
CDH5 levels and the CDH5 glycosylation represent biomarker tests that distinguish patients with metastatic breast cancer from those that remain metastasis-free. The test reached optimal sensitivity and specificity in ER-positive cancers with vascular invasion.
先前的一项糖蛋白质组学研究表明，在同时评估蛋白质水平和糖基化状态时，钙黏蛋白-5（CDH5）是转移性乳腺癌的血清学标志物。在本研究中，我们旨在进一步验证CDH5作为乳腺癌进展生物标志物的效用。
对乳腺癌患者的血清样本进行巢式病例对照研究，其中n = 52例在诊断后5年内发生远处转移复发，n = 60例无复发。采用酶联免疫吸附测定（ELISA）定量患者血清CDH5水平，并通过锥螺凝集素（HPA）结合评估糖基化。确定与转移和生物标志物水平升高相关的临床病理、治疗和生活方式因素。
CDH5水平升高（P = 0.028）以及CDH5:HPA结合比率升高（P = 0.007）可区分转移性疾病患者和无转移患者。多变量分析表明，CDH5:HPA比率与远处转移形成之间的关联是由雌激素受体（ER+）阳性且伴有血管侵犯（VI+）的癌症患者驱动的。
CDH5水平和CDH5糖基化代表了区分转移性乳腺癌患者和无转移患者的生物标志物检测。该检测在伴有血管侵犯的ER阳性癌症中达到了最佳敏感性和特异性。
