Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error.
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 morbidit...
| Publicado en: | British Journal of Cancer Vol. 111; no. 6; pp. 1201 - 1213 |
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| Autores principales: | , , , , , , , , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Springer Nature
9/9/2014
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=103887287&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 103887287 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00070920 1XV jtl: British Journal of Cancer issn: 00070920 maglogo: Y pubinfo: dt: 9/9/2014 vid: 111 iid: 6 pid: 2579 pub: Springer Nature place: Dordrecht, <Blank> artinfo: ui: 103887287 NLM25032733 2012726151 10.1038/bjc.2014.396 NLM25032733 103887287 ppf: 1201 ppct: 12 formats: tig: atl: Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error. aug: au: Shipitsin, M Small, C Choudhury, S Giladi, E Friedlander, S Nardone, J Hussain, S Hurley, A D Ernst, C Huang, Y E Chang, H Nifong, T P Rimm, D L Dunyak, J Loda, M Berman, D M Blume-Jensen, P affil: Metamark Genetics Inc., Cambridge, MA 02142, USA. sug: subj: Prostate Pathology Prostatic Neoplasms Mortality Prostatic Neoplasms Pathology Tumor Markers, Biological Analysis Muscle Proteins Analysis Aged Transferases Analysis Pharmacokinetics Biopsy, Needle Proteins Analysis Prospective Studies Human Image Processing, Computer Assisted Male Membrane Proteins Analysis Middle Age Prognosis Neoplasm Staging Metabolism Prostate Prostatic Neoplasms Proteomics ROC Curve Proteins Metabolism Selection Bias Carrier Proteins Analysis Tissue Array Analysis Aged: 65+ years Middle Aged: 45-64 years Male ab: 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. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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