Ueo H, Sugimachi K, Gorges T M, Bartkowiak K, Yokobori T, Müller V, Shinden Y, Ueda M, Ueo H, Mori M, Kuwano H, Maehara Y, Ohno S, Pantel K, Mimori K
1] Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 874-0838, Japan [2] Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
Br J Cancer. 2015 Apr 28;112(9):1519-26. doi: 10.1038/bjc.2015.132. Epub 2015 Apr 16.
Identification of promising biomarkers that predict the prognosis of patients with breast cancer is needed. In this study, we hypothesised that the expression of the epithelial-mesenchymal transition-related biomarker plastin3 (PLS3) in peripheral blood could be a prognostic factor in breast cancer.
We examined PLS3 expression in breast cancer cell lines with epithelial and mesenchymal traits and in circulating tumour cells (CTCs) obtained from the peripheral blood of breast cancer patients. We investigated PLS3 expression in the peripheral blood of 594 patients with breast cancer to evaluate the clinical significance of PLS3 expression.
Robust PLS3 expression was observed in different breast cancer cell lines (Hs578t, MCF-7, MDA-MB-468, and MDA-MB-231) as well as in a bone marrow derived cancer cell line (BC-M1). In both the training (n=298) and validation (n=296) sets, PLS3 expression was observed in CTCs of patients with breast cancer. PLS3-positive patients showed significantly poorer overall and disease-free survival than PLS3-negative patients (P=0.0001 and 0.003, respectively). Subset analysis revealed that this prognostic biomarker was relevant in patients with stage I-III cancer, particularly in patients with luminal-type and triple-negative-type tumours.
These data demonstrated that PLS3 was expressed in CTCs undergoing the epithelial-mesenchymal transition in patients with breast cancer. Furthermore, PLS3 may be an excellent biomarker for identifying groups at risk of recurrence or with a poor prognosis.
需要鉴定出能够预测乳腺癌患者预后的有前景的生物标志物。在本研究中,我们假设外周血中上皮-间质转化相关生物标志物丝束蛋白3(PLS3)的表达可能是乳腺癌的一个预后因素。
我们检测了具有上皮和间质特征的乳腺癌细胞系以及从乳腺癌患者外周血中获得的循环肿瘤细胞(CTC)中PLS3的表达。我们调查了594例乳腺癌患者外周血中PLS3的表达,以评估PLS3表达的临床意义。
在不同的乳腺癌细胞系(Hs578t、MCF-7、MDA-MB-468和MDA-MB-231)以及一个骨髓源性癌细胞系(BC-M1)中均观察到了强烈的PLS3表达。在训练集(n = 298)和验证集(n = 296)中,均在乳腺癌患者的CTC中观察到了PLS3表达。PLS3阳性患者的总生存期和无病生存期均显著低于PLS3阴性患者(分别为P = 0.0001和0.003)。亚组分析显示,这种预后生物标志物在I-III期癌症患者中具有相关性,特别是在管腔型和三阴性型肿瘤患者中。
这些数据表明,PLS3在乳腺癌患者经历上皮-间质转化的CTC中表达。此外,PLS3可能是用于识别复发风险或预后不良群体的优秀生物标志物。