转移性乳腺癌患者血清 Tau 蛋白水平的预后价值及其与脑转移的相关性。
The prognostic value of the Tau protein serum level in metastatic breast cancer patients and its correlation with brain metastases.
机构信息
Department of Medical Oncology, Institut du Cancer de Montpellier, University of Montpellier, 208 Avenue des Apothicaires, 34298, Montpellier, France.
Laboratoire de Biochimie et Protéomique Clinique, University of Montpellier, Institute of Regenerative Medicine - Biotherapy IRMB, CHU Montpellier, INSERM, 80 Avenue Augustin Fliche, 34295, Montpellier, France.
出版信息
BMC Cancer. 2019 Jan 30;19(1):110. doi: 10.1186/s12885-019-5287-z.
BACKGROUND
Metastatic breast cancer (MBC) prognosis is variable, depending on several clinical and biological factors. A better prediction of a patient's outcome could allow for a more accurate choice of treatments. The role of serum biomarkers in predicting outcome remains unclear in this setting. Tau, a microtubule-associated protein, is a neuronal marker that is also expressed in normal breast epithelial cells and cancer cells. Its tissue expression is associated with prognosis in MBC. However, the prognostic value of Tau serum levels in these patients is unknown. We aimed at evaluating the prognostic value of Tau (and other classical biomarkers) in MBC patients, and to assess its association with the presence of brain metastases (BM).
METHODS
244 MBC patients treated at our institution (2007-2015) were retrospectively selected. The usual MBC clinical and pathological variables were collected, altogether with CA15-3, CEA and HER2 extra-cellular domain (ECD) serum levels. Tau serum levels were measured with a novel immunoassay (digital ELISA) using Single Molecule Array (Simoa) technology. Overall survival (OS) was estimated with the Kaplan-Meier method. To investigate prognostic factors, a multivariate analysis was performed. Cut-offs were set using the Youden index method associated with receiver-operating characteristics (ROC) curves to evaluate the accuracy of biomarkers to identify patients with BM.
RESULTS
With a median follow-up of 40.8 months, median OS was 15.5 months (95%CI 12.4-20.2). Elevated serum levels of Tau were independently associated with a poor outcome in the whole population as well as in patients with (n = 86) and without BM (n = 158). Median serum Tau levels tended to be higher in patients with BM (p = 0.23). In univariate analysis, patients with BM had an increased risk of serum Tau > 3.17 pg/mL (OR = 2.2, p = 0.049). In multivariate analysis, high values of Tau (OR = 3.98, p = 0.034) accurately identified patients with BM in our cohort.
CONCLUSIONS
Tau is a new biomarker of interest in MBC. Its serum level could represent an independent prognostic factor in these patients (both with and without BM). It also seems to be associated with the presence of BM. A validation of these results in an independent set of MBC patients is necessary to confirm these findings.
背景
转移性乳腺癌（MBC）的预后因多种临床和生物学因素而异。对患者预后的更好预测可以更准确地选择治疗方法。在这种情况下，血清生物标志物在预测结局中的作用尚不清楚。Tau 是一种微管相关蛋白，也是神经元标志物，在正常乳腺上皮细胞和癌细胞中也有表达。其组织表达与 MBC 的预后相关。然而，Tau 血清水平在这些患者中的预后价值尚不清楚。我们旨在评估 Tau（和其他经典生物标志物）在 MBC 患者中的预后价值，并评估其与脑转移（BM）存在的相关性。
方法
回顾性选择我院 2007-2015 年治疗的 244 例 MBC 患者。收集了通常的 MBC 临床和病理变量，以及 CA15-3、CEA 和 HER2 细胞外结构域（ECD）的血清水平。使用单分子阵列（Simoa）技术的新型免疫测定法（数字 ELISA）测量 Tau 血清水平。使用 Kaplan-Meier 方法估计总生存期（OS）。为了研究预后因素，进行了多变量分析。使用与接收者操作特性（ROC）曲线相关的约登指数法设置截止值，以评估生物标志物识别 BM 患者的准确性。
结果
中位随访 40.8 个月，中位 OS 为 15.5 个月（95%CI 12.4-20.2）。在整个人群以及有（n=86）和没有 BM（n=158）的患者中，升高的 Tau 血清水平独立与不良预后相关。有 BM 的患者的 Tau 血清水平中位数倾向于较高（p=0.23）。在单变量分析中，BM 患者 Tau>3.17pg/ml 的风险增加（OR=2.2，p=0.049）。在多变量分析中，Tau 值较高（OR=3.98，p=0.034）准确地识别了我们队列中的 BM 患者。
结论
Tau 是 MBC 中一种新的有前途的生物标志物。其血清水平可能是这些患者（有和无 BM）的独立预后因素。它似乎也与 BM 的存在有关。需要在一组独立的 MBC 患者中验证这些结果，以证实这些发现。
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