Comparative proteome analysis revealing an 11-protein signature for aggressive triple-negative breast cancer.
Comparative proteome analysis revealing an 11-protein signature for aggressive triple-negative breast cancer.
复制标题
DOI：
10.1093/jnci/djt376
复制
发表时间：
2014-02
期刊：
影响因子：
--
通讯作者：
Umar A
中科院分区：
文献类型：
--
作者：
Liu NQ;Stingl C;Look MP;Smid M;Braakman RB;De Marchi T;Sieuwerts AM;Span PN;Sweep FC;Linderholm BK;Mangia A;Paradiso A;Dirix LY;Van Laere SJ;Luider TM;Martens JW;Foekens JA;Umar A
三阴性乳腺癌（TNBC）患者的临床预后变化很大。本研究旨在确定和验证TNBC患者的预后蛋白标记，以减少不必要的辅助全身治疗。从126例淋巴结阴性和未接受辅助治疗的TNBC患者中收集冷冻原发肿瘤。这些样本被用于两个系列的全球蛋白质组分析：内部培训（n = 63）和多中心测试（n = 63）集。术后至少5年无远处转移的患者被定义为预后良好。进行Cox回归分析以形成预后特征，并进行独立验证。所有统计检验均为双侧检验。在训练集中（预后良好患者的中位随访时间为117个月）建立了一个11蛋白特征，随后在测试集中（预后良好患者的中位随访时间为108个月）进行了验证，结果显示，对预后不良患者的敏感性为89.5%(95%置信区间[CI] = 69.2% ~ 98.1%)，特异性为70.5% (95% CI = 61.7% ~ 74.2%)，阳性预测值为56.7% (95% CI = 43.8% ~ 62.1%)，阴性预测值为93.9% （95% CI = 82.3% ~ 98.9%）。单因素分析（HR = 13.15; 95% CI = 3.03 ~ 57.07; P = 0.001）和多因素分析（HR = 12.45; 95% CI = 2.67 ~ 58.11; P = 0.001）中预测预后差的患者发生远处转移的风险高于预测预后好的患者。此外，预测预后不良组的乳腺癌特异性死亡率在统计学上显著增加。使用我们的签名作为指导，与传统的预后指南相比，超过60%的患者将免除不必要的辅助化疗。我们报告了第一个验证的蛋白质组学特征来评估临床TNBC的自然病程。
Clinical outcome of patients with triple-negative breast cancer (TNBC) is highly variable. This study aims to identify and validate a prognostic protein signature for TNBC patients to reduce unnecessary adjuvant systemic therapy. Frozen primary tumors were collected from 126 lymph node–negative and adjuvant therapy–naive TNBC patients. These samples were used for global proteome profiling in two series: an in-house training (n = 63) and a multicenter test (n = 63) set. Patients who remained free of distant metastasis for a minimum of 5 years after surgery were defined as having good prognosis. Cox regression analysis was performed to develop a prognostic signature, which was independently validated. All statistical tests were two-sided. An 11-protein signature was developed in the training set (median follow-up for good-prognosis patients = 117 months) and subsequently validated in the test set (median follow-up for good-prognosis patients = 108 months) showing 89.5% sensitivity (95% confidence interval [CI] = 69.2% to 98.1%), 70.5% specificity (95% CI = 61.7% to 74.2%), 56.7% positive predictive value (95% CI = 43.8% to 62.1%), and 93.9% negative predictive value (95% CI = 82.3% to 98.9%) for poor-prognosis patients. The predicted poor-prognosis patients had higher risk to develop distant metastasis than the predicted good-prognosis patients in univariate (hazard ratio [HR] = 13.15; 95% CI = 3.03 to 57.07; P = .001) and multivariable (HR = 12.45; 95% CI = 2.67 to 58.11; P = .001) analysis. Furthermore, the predicted poor-prognosis group had statistically significantly more breast cancer–specific mortality. Using our signature as guidance, more than 60% of patients would have been exempted from unnecessary adjuvant chemotherapy compared with conventional prognostic guidelines. We report the first validated proteomic signature to assess the natural course of clinical TNBC.
登录
查看更多内容
影响因子：
9.9
作者：
通讯作者：
--
DOI：
10.1016/j.bbrc.2012.11.103
发表时间：
2013-01-11
影响因子：
3.1
作者：
Lubecka-Pietruszewska, Katarzyna;Kaufman-Szymczyk, Agnieszka;Fabianowska-Majewska, Krystyna
通讯作者：
Fabianowska-Majewska, Krystyna
供临床医生使用的铁蛋白。
影响因子：
7.4
作者：
Knovich, Mary Ann;Storey, Jonathan A.;Coffman, Lan G.;Torti, Suzy V.;Torti, Frank M.
通讯作者：
Torti, Frank M.
影响因子：
3.7
作者：
Takahashi, Tsuyoshi;Sonobe, Makoto;Date, Hiroshi
通讯作者：
Date, Hiroshi
影响因子：
3.7
作者：
Kuo WH;Chang YY;Lai LC;Tsai MH;Hsiao CK;Chang KJ;Chuang EY
通讯作者：
Chuang EY