Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error
| العنوان: | Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error |
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| المؤلفون: | Julie Nardone, Peter Blume-Jensen, Massimo Loda, Christina Ernst, Shaun A. Hussain, Thomas P. Nifong, David L. Rimm, S Friedlander, Sibgat Choudhury, Y E Huang, Michail Shipitsin, Catherine B. Small, David M. Berman, H. Chang, Aeron D. Hurley, J. Dunyak, Eldar Giladi |
| المصدر: | British Journal of Cancer |
| بيانات النشر: | Nature Publishing Group, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1532-1827 0007-0920 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7ef42de7cd2594c8dbcc3bd61e5370a8Test http://europepmc.org/articles/PMC4453845Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7ef42de7cd2594c8dbcc3bd61e5370a8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15321827 00070920 |
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