Zeidan Bashar, Jackson Thomas R, Larkin Samantha E T, Cutress Ramsey I, Coulton Gary R, Ashton-Key Margaret, Murray Nick, Packham Graham, Gorgoulis Vassilis, Garbis Spiros D, Townsend Paul A
Cancer Sciences Unit, University of Southampton, Southampton, UK.
Faculty Institute for Cancer Sciences, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.
Oncotarget. 2015 Aug 28;6(25):21421-7. doi: 10.18632/oncotarget.4070.
Breast cancers are the most common cancer-affecting women; critically the identification of novel biomarkers for improving early detection, stratification and differentiation from benign tumours is important for the reduction of morbidity and mortality.To identify and functionally characterise potential biomarkers, we used mass spectrometry (MS) to analyse serum samples representing control, benign breast disease (BBD) and invasive breast cancer (IDC) patients. Complementary and multidimensional proteomic approaches were used to identify and validate novel serum markers.Annexin A3 (ANX A3) was found to be differentially expressed amongst different breast pathologies. The diagnostic value of serum ANX A3 was subsequently validated by ELISA in an independent serum set representing the three groups. Here, ANX A3 was significantly upregulated in the benign disease group sera compared with other groups (P < 0.0005).In addition, paired breast tissue immunostaining confirmed that ANX A3 was abundantly expressed in benign and to a lesser extent malignant neoplastic epithelium. Finally, we illustrated ANX A3 expression in cell culture lysates and conditioned media from neoplastic breast cell lines, and its role in neoplastic breast cell migration in vitro.This study confirms the novel role of ANX A3 as a mammary biomarker, regulator and therapeutic target.
乳腺癌是影响女性的最常见癌症；至关重要的是，识别用于改善早期检测、分层以及与良性肿瘤鉴别的新型生物标志物对于降低发病率和死亡率非常重要。为了识别并对潜在生物标志物进行功能表征，我们使用质谱分析法（MS）分析了代表对照、良性乳腺疾病（BBD）和浸润性乳腺癌（IDC）患者的血清样本。采用互补和多维蛋白质组学方法来识别并验证新型血清标志物。发现膜联蛋白A3（ANX A3）在不同乳腺病理状态中存在差异表达。随后，通过酶联免疫吸附测定法（ELISA）在代表这三组的独立血清组中验证了血清ANX A3的诊断价值。在此，与其他组相比，良性疾病组血清中的ANX A3显著上调（P < 0.0005）。此外，配对乳腺组织免疫染色证实ANX A3在良性肿瘤上皮中大量表达，在恶性肿瘤上皮中的表达程度较低。最后，我们展示了ANX A3在乳腺肿瘤细胞系的细胞培养裂解物和条件培养基中的表达情况，以及它在体外乳腺肿瘤细胞迁移中的作用。本研究证实了ANX A3作为乳腺生物标志物、调节剂和治疗靶点的新作用。
