Article

Anchoring proteins encounter mitotic kinases

Howard Hughes Medical Institute
Cell cycle (Georgetown, Tex.) (Impact Factor: 5.01). 03/2013; 12(6). DOI: 10.4161/cc.24192
Source: PubMed
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    ABSTRACT: Background:Key challenges of biopsy-based determination of prostate cancer aggressiveness include tumour heterogeneity, biopsy-sampling error, and variations in biopsy interpretation. The resulting uncertainty in risk assessment leads to significant overtreatment, with associated costs and morbidity. We developed a performance-based strategy to identify protein biomarkers predictive of prostate cancer aggressiveness and lethality regardless of biopsy-sampling variation.Methods:Prostatectomy samples from a large patient cohort with long follow-up were blindly assessed by expert pathologists who identified the tissue regions with the highest and lowest Gleason grade from each patient. To simulate biopsy-sampling error, a core from a high- and a low-Gleason area from each patient sample was used to generate a 'high' and a 'low' tumour microarray, respectively.Results:Using a quantitative proteomics approach, we identified from 160 candidates 12 biomarkers that predicted prostate cancer aggressiveness (surgical Gleason and TNM stage) and lethal outcome robustly in both high- and low-Gleason areas. Conversely, a previously reported lethal outcome-predictive marker signature for prostatectomy tissue was unable to perform under circumstances of maximal sampling error.Conclusions:Our results have important implications for cancer biomarker discovery in general and development of a sampling error-resistant clinical biopsy test for prediction of prostate cancer aggressiveness.British Journal of Cancer advance online publication, 17 July 2014; doi:10.1038/bjc.2014.396 www.bjcancer.com.
    British Journal of Cancer 07/2014; 111(6). DOI:10.1038/bjc.2014.396 · 4.82 Impact Factor

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