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Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error
- Source :
- British Journal of Cancer
- Publication Year :
- 2014
- Publisher :
- Nature Publishing Group, 2014.
-
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.
- Subjects :
- Oncology
Male
Proteomics
Cancer Research
Pathology
sampling error
Smad2 Protein
Prostate cancer
Prostate
Image Processing, Computer-Assisted
Actinin
Phosphorylation
Smad4 Protein
Ribosomal Protein S6
medicine.diagnostic_test
Middle Aged
prostate cancer
Cullin Proteins
DNA-Binding Proteins
medicine.anatomical_structure
Area Under Curve
Identification (biology)
medicine.medical_specialty
Tumour heterogeneity
Biopsy, Fine-Needle
Mitochondrial Proteins
Internal medicine
Biopsy
medicine
Biomarkers, Tumor
Humans
biopsy
HSP70 Heat-Shock Proteins
Molecular Diagnostics
Selection Bias
Aged
Neoplasm Staging
Neoplasm Grading
Alkyl and Aryl Transferases
business.industry
Voltage-Dependent Anion Channel 1
biomarkers
Membrane Proteins
Prostatic Neoplasms
medicine.disease
ROC Curve
Tissue Array Analysis
RNA-Binding Protein FUS
Lethality
prognosis
tumour heterogeneity
Y-Box-Binding Protein 1
business
Follow-Up Studies
Subjects
Details
- Language :
- English
- ISSN :
- 15321827 and 00070920
- Volume :
- 111
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- British Journal of Cancer
- Accession number :
- edsair.doi.dedup.....7ef42de7cd2594c8dbcc3bd61e5370a8