Dataset Information

Evaluation of prognostic and predictive value of microtubule associated protein tau in two independent cohorts.

ABSTRACT:

Introduction

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.

Methods

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.

Results

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).

Conclusions

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.

SUBMITTER: Baquero MT

PROVIDER: S-EPMC3262195 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Publications

Evaluation of prognostic and predictive value of microtubule associated protein tau in two independent cohorts.

Baquero Maria T MT Lostritto Karen K Gustavson Mark D MD Bassi Kimberly A KA Appia Franck F Camp Robert L RL Molinaro Annette M AM Harris Lyndsay N LN Rimm David L DL

Breast cancer research : BCR 20111102 5

<h4>Introduction</h4>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.<h4>Methods</h4>MAP-tau expression was evaluated in the retrospective Yale University breast ...[more]

PMID: 21888627

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Project description:BackgroundLiver function tests might predict the risk of type 2 diabetes. An independent study evaluating utility of these markers compared with an existing prediction model is yet lacking.Methods and findingsWe performed a case-cohort study, including random subcohort (6.5%) from 38,379 participants with 924 incident diabetes cases (the Dutch contribution to the European Prospective Investigation Into Cancer and Nutrition, EPIC-NL, the Netherlands), and another population-based cohort study including 7,952 participants with 503 incident cases (the Prevention of Renal and Vascular End-stage Disease, PREVEND, Groningen, the Netherlands). We examined predictive value of combination of the Liver function tests (gamma-glutamyltransferase, alanine aminotransferase, aspartate aminotransferase and albumin) above validated models for 7.5-year risk of diabetes (the Cooperative Health Research in the Region of Augsburg, the KORA study). Basic model includes age, sex, BMI, smoking, hypertension and parental diabetes. Clinical models additionally include glucose and uric acid (model1) and HbA1c (model2). In both studies, addition of Liver function tests to the basic model improved the prediction (C-statistic by~0.020; NRI by~9.0%; P<0.001). In the EPIC-NL case-cohort study, addition to clinical model1 resulted in statistically significant improvement in the overall population (C-statistic?=?+0.009; P<0.001; NRI?=?8.8%; P<0.001), while addition to clinical model 2 yielded marginal improvement limited to men (C-statistic?=?+0.007; P?=?0.06; NRI?=?3.3%; P?=?0.04). In the PREVEND cohort study, addition to clinical model 1 resulted in significant improvement in the overall population (C-statistic change?=?0.008; P?=?0.003; NRI?=?3.6%; P?=?0.03), with largest improvement in men (C-statistic change?=?0.013; P?=?0.01; NRI?=?5.4%; P?=?0.04). In PREVEND, improvement compared to clinical model 2 could not be tested because of lack of HbA1c data.ConclusionsLiver function tests modestly improve prediction for medium-term risk of incident diabetes above basic and extended clinical prediction models, only if no HbA1c is incorporated. If data on HbA1c are available, Liver function tests have little incremental predictive value, although a small benefit may be present in men.

Dataset Information

Evaluation of prognostic and predictive value of microtubule associated protein tau in two independent cohorts.

Introduction

Methods

Results

Conclusions

Publications

Evaluation of prognostic and predictive value of microtubule associated protein tau in two independent cohorts.

Similar Datasets

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