Evaluation of prognostic and predictive value of microtubule associated protein tau in two independent cohorts.
Evaluation of prognostic and predictive value of microtubule associated protein tau in two independent cohorts.
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DOI：
10.1186/bcr2937
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发表时间：
2011-11-02
期刊：
影响因子：
--
通讯作者：
Rimm DL
中科院分区：
文献类型：
--
作者：
Baquero MT;Lostritto K;Gustavson MD;Bassi KA;Appia F;Camp RL;Molinaro AM;Harris LN;Rimm DL
微管相关蛋白 (MAP) 内源性调节微管稳定性，并已被报道为紫杉烷反应的预后和预测标记物。微管稳定剂 MAP-tau 显示出相互矛盾的结果。我们定量评估了两个独立乳腺癌队列中的 MAP-tau 表达，以确定该生物标志物的预后和预测价值。使用组织微阵列在回顾性耶鲁大学乳腺癌队列 (n = 651) 中评估 MAP-tau 表达，也在 TAX 307 队列中评估了 MAP-tau 表达，TAX 307 队列是一项随机 TAC 与 FAC 化疗 (n = 140) 的临床试验，使用传统的全组织切片。使用定量免疫荧光的 AQUA 方法测量表达。评分与临床病理变量、生存率和治疗反应相关。使用 Cox 单变量分析对耶鲁队列进行的评估表明，肿瘤的总生存期 (OS) 有所改善，MAP-tau 高表达与总生存期 (OS) 之间呈正相关（HR = 0.691，95% CI = 0.489-0.974；P = 0.004）。 Kaplan Meier 分析显示，MAP-tau 高表达的患者有 65% 的 10 年生存率，而低表达的患者为 52% (P = .006)。在 TAX 307 中，无论治疗组如何，高表达与显着较长的中位肿瘤进展时间 (TTP) 相关（33.0 个月与 23.4 个月，P = 0.010），平均 TTP 为 31.2 个月。 MAP-tau 表达 (P = 0.518) 或治疗组 (P = 0.584) 的缓解率没有差异。 MAP-tau 表达的定量测量在两个队列中都具有预后价值，高表达与较长的 TTP 和 OS 相关。没有观察到低 MAP-tau 组与高 MAP-tau 组的治疗组或缓解率差异，表明 MAP-tau 与紫杉烷类药物的反应无关，并且不是基于紫杉烷类化疗的有用预测标记。
Microtubule associated proteins (MAPs) endogenously regulate microtubule stabilization and have been reported as prognostic and predictive markers for taxane response. The microtubule stabilizer, MAP-tau, has shown conflicting results. We quantitatively assessed MAP-tau expression in two independent breast cancer cohorts to determine prognostic and predictive value of this biomarker. MAP-tau expression was evaluated in the retrospective Yale University breast cancer cohort (n = 651) using tissue microarrays and also in the TAX 307 cohort, a clinical trial randomized for TAC versus FAC chemotherapy (n = 140), using conventional whole tissue sections. Expression was measured using the AQUA method for quantitative immunofluorescence. Scores were correlated with clinicopathologic variables, survival, and response to therapy. Assessment of the Yale cohort using Cox univariate analysis indicated an improved overall survival (OS) in tumors with a positive correlation between high MAP-tau expression and overall survival (OS) (HR = 0.691, 95% CI = 0.489-0.974; P = 0.004). Kaplan Meier analysis showed 10-year survival for 65% of patients with high MAP-tau expression compared to 52% with low expression (P = .006). In TAX 307, high expression was associated with significantly longer median time to tumor progression (TTP) regardless of treatment arm (33.0 versus 23.4 months, P = 0.010) with mean TTP of 31.2 months. Response rates did not differ by MAP-tau expression (P = 0.518) or by treatment arm (P = 0.584). Quantitative measurement of MAP-tau expression has prognostic value in both cohorts, with high expression associated with longer TTP and OS. Differences by treatment arm or response rate in low versus high MAP-tau groups were not observed, indicating that MAP-tau is not associated with response to taxanes and is not a useful predictive marker for taxane-based chemotherapy.
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DOI：
10.1083/jcb.138.5.1067
发表时间：
1997-09-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Felgner H;Frank R;Biernat J;Mandelkow EM;Mandelkow E;Ludin B;Matus A;Schliwa M
通讯作者：
Schliwa M
影响因子：
3.4
作者：
Choi, M. C.;Raviv, U.;Safinya, C. R.
通讯作者：
Safinya, C. R.
影响因子：
45.3
作者：
Welsh, Allison W.;Moeder, Christopher B.;Rimm, David L.
通讯作者：
Rimm, David L.
影响因子：
11.5
作者：
Andre, Fabrice;Hatzis, Christos;Pusztai, Lajos
通讯作者：
Pusztai, Lajos
影响因子：
45.3
作者：
De Laurentiis, Michele;Cancello, Giuseppe;De Placido, Sabino
通讯作者：
De Placido, Sabino