Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error.

M. Shipitsin, C. Small, S. Choudhury, E. Giladi, S. Friedlander, J. Nardone, S. Hussain, A. D. Hurley, C. Ernst, Y. E. Huang, H. Chang, T. P. Nifong, D. L. Rimm, J. Dunyak, M. Loda, D. M. Berman, P. Blume-Jensen

Research output: Contribution to journalArticlepeer-review

Abstract

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. 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. 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. 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.

Original languageEnglish (US)
Pages (from-to)1201-1212
Number of pages12
JournalBritish Journal of Cancer
Volume111
Issue number6
DOIs
StatePublished - 2014
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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