乳腺癌中 cMET 和磷酸化 cMET 蛋白水平与生存结局。
cMET and phospho-cMET protein levels in breast cancers and survival outcomes.
机构信息
Department of Hematology/Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
出版信息
Clin Cancer Res. 2012 Apr 15;18(8):2269-77. doi: 10.1158/1078-0432.CCR-11-2830. Epub 2012 Feb 28.
PURPOSE
To evaluate cMET (mesenchymal-epithelial transition factor gene) and phospho-cMET (p-cMET) levels in breast cancer subtypes and its impact on survival outcomes.
EXPERIMENTAL DESIGN
We measured protein levels of cMET and p-cMET in 257 breast cancers using reverse phase protein array. Regression tree method and Martingale residual plots were applied to find best cutoff point for high and low levels. Kaplan-Meier survival curves were used to estimate relapse-free (RFS) and overall (OS) survival. Cox proportional hazards models were fit to determine associations of cMET/p-cMET with outcomes after adjustment for other characteristics.
RESULTS
Median age was 51 years. There were 140 (54.5%) hormone receptor (HR) positive, 53 (20.6%) HER2 positive, and 64 (24.9%) triple-negative tumors. Using selected cutoffs, 181 (70.4%) and 123 (47.9%) cancers had high levels of cMET and p-cMET, respectively. There were no significant differences in mean expression of cMET (P < 0.128) and p-cMET (P < 0.088) by breast cancer subtype. Dichotomized cMET and p-cMET level was a significant prognostic factor for RFS [HR: 2.44, 95% confidence interval (CI): 1.34-4.44, P = 0.003 and HR: 1.64, 95% CI: 1.04-2.60, P = 0.033] and OS (HR: 3.18, 95% CI: 1.43-7.11, P = 0.003 and HR: 1.92, 95% CI: 1.08-3.44, P = 0.025). Within breast cancer subtypes, high cMET levels were associated with worse RFS (P = 0.014) and OS (P = 0.006) in HR-positive tumors, and high p-cMET levels were associated with worse RFS (P = 0.019) and OS (P = 0.014) in HER2-positive breast cancers. In multivariable analysis, patients with high cMET had a significantly higher risk of recurrence (HR: 2.06, 95% CI: 1.08-3.94, P = 0.028) and death (HR: 2.81, 95% CI: 1.19-6.64, P = 0.019). High p-cMET level was associated with higher risk of recurrence (HR: 1.79, 95% CI: 1.08-2.95.77, P = 0.020).
CONCLUSIONS
High levels of cMET and p-cMET were seen in all breast cancer subtypes and correlated with poor prognosis.
目的
评估乳腺癌亚型中 cMET（间质-上皮转化因子基因）和磷酸化 cMET（p-cMET）水平及其对生存结果的影响。
实验设计
我们使用反相蛋白阵列测量了 257 例乳腺癌中 cMET 和 p-cMET 的蛋白水平。回归树方法和 Martingale 残差图用于寻找高、低水平的最佳截断点。Kaplan-Meier 生存曲线用于估计无复发生存（RFS）和总生存（OS）。Cox 比例风险模型用于确定 cMET/p-cMET 与其他特征调整后的结局之间的关联。
结果
中位年龄为 51 岁。140 例（54.5%）为激素受体（HR）阳性，53 例（20.6%）为 HER2 阳性，64 例（24.9%）为三阴性肿瘤。使用选定的截断值，分别有 181 例（70.4%）和 123 例（47.9%）癌症的 cMET 和 p-cMET 水平较高。乳腺癌亚型之间 cMET（P < 0.128）和 p-cMET（P < 0.088）的平均表达无显著差异。cMET 和 p-cMET 水平的二分法是 RFS 的显著预后因素[HR：2.44，95%置信区间（CI）：1.34-4.44，P = 0.003 和 HR：1.64，95% CI：1.04-2.60，P = 0.033]和 OS（HR：3.18，95% CI：1.43-7.11，P = 0.003 和 HR：1.92，95% CI：1.08-3.44，P = 0.025）。在乳腺癌亚型内，高 cMET 水平与 HR 阳性肿瘤的 RFS（P = 0.014）和 OS（P = 0.006）较差相关，高 p-cMET 水平与 HER2 阳性乳腺癌的 RFS（P = 0.019）和 OS（P = 0.014）较差相关。多变量分析显示，高 cMET 患者的复发风险显著升高（HR：2.06，95%CI：1.08-3.94，P = 0.028）和死亡风险（HR：2.81，95%CI：1.19-6.64，P = 0.019）。高 p-cMET 水平与更高的复发风险相关（HR：1.79，95%CI：1.08-2.95，P = 0.020）。
结论
所有乳腺癌亚型中均可见 cMET 和 p-cMET 水平升高，并与预后不良相关。
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