Dataset Information

Proteins from formalin-fixed paraffin-embedded prostate cancer sections that predict the risk of metastatic disease

ABSTRACT: Purpose: Prostate cancer is the most frequently diagnosed cancer in men and the third leading cause of cancer related deaths among men living in developed countries. Biomarkers that predict disease outcome at the time of initial diagnosis would aid management of the disease. Experimental design: Proteins extracted from formalin-fixed paraffin-embeddded sections were identified either using LC-MALDI MS/MS of tryptic digests or after separation by one- or two-dimensional electrophoresis. A list of potential biomarker candidates, based on proposed associations with prostate cancer, was derived from the 320 identified proteins. Results: Four of the candidates: annexin A2, peroxiredoxin-1, prostate-specific antigen and zinc-alpha-2-glycoprotein, were examined by Western blotting of extracts of biopsies from men whom there was 10-year disease outcome data. Multiplexed Western blotting using cocktails of antibodies and fluor-labeled detection reagents showed that annexin A2 provided the best prediction of risk of metastatic disease. Conclusions and clinical relevance: This pilot study indicates that tumour expression of ANXA2 in diagnostic biopsies of a prostate cancer is predictive for the metastatic potential of that cancer. The potential of protein profiling of each cancer is to lead to an overall reduction in mortality from metastatic prostate cancer as well as reduced treatment associated morbidity.

INSTRUMENT(S): 4800 Proteomics Analyzer

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Prostate Gland, Epithelial Cell

DISEASE(S): Prostate Adenocarcinoma

SUBMITTER: Danyl Mclauchlan

LAB HEAD: Bill Jordan

PROVIDER: PXD000963 | Pride | 2015-09-14

REPOSITORIES: pride

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Dataset's files

Source:

			Action	DRS
	20100713_MOBBCellLysate_LCMALDI.zip	Other
	20100714_MOBBCellLysate_LCMALDI.zip	Other
	20100721_MOBBCellLysate_LCMALDI.zip	Other
	20100722_MOBBCellLysate_LCMALDI.zip	Other
	20100816MOBBSliceandDice.zip	Other

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Proteins from formalin-fixed paraffin-embedded prostate cancer sections that predict the risk of metastatic disease.

Dunne Jonathan C JC Lamb David S DS Delahunt Brett B Murray Judith J Bethwaite Peter P Ferguson Peter P Nacey John N JN Sondhauss Sven S Jordan T William TW

Clinical proteomics 20150916 1

<h4>Background</h4>Prostate cancer is the most frequently diagnosed cancer in men and the third leading cause of cancer related deaths among men living in developed countries. Biomarkers that predict disease outcome at the time of initial diagnosis would substantially aid disease management.<h4>Results</h4>Proteins extracted from formalin-fixed paraffin-embedded tissue were identified using nanoflow liquid chromatography-MALDI MS/MS or after separation by one- or two-dimensional electrophoresis. ...[more]

PMID: 26388710

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Project description:Current prostate cancer prognostic models are based on pre-treatment prostate-specific antigen (PSA) levels, biopsy Gleason score, and clinical staging but in practice are inadequate to accurately predict clinical disease progression. Hence, we sought to develop a molecular panel for prostate cancer progression by reasoning that molecular profiles might further improve current clinical models. We analyzed a Swedish Watchful Waiting cohort (1977â1999) with up to 30 years of clinical follow up using a novel method for gene expression profiling. This cDNA-mediated annealing, selection, ligation, and extension (DASL) method enabled the use of formalin-fixed paraffin-embedded transurethral resection of prostate (TURP) samples taken at the time of the initial diagnosis. We determined the expression profiles of 6100 genes for 281 men divided in two extreme groups: men who died of prostate cancer or developed metastases and men who survived more than 10 years without metastases (lethals and indolents, respectively). Several models using clinical and molecular features were evaluated for their ability to distinguish lethal from indolent cases. Surprisingly, none of the predictive models using molecular profiles significantly improved over models using clinical variables only. We reasoned that tumor sampling might preclude the identification of the dominant metastatic nodule. Additional computational analysis confirmed that molecular heterogeneity within both the lethal and indolent classes is widespread in prostate cancer as compared to other types of tumors. Thus the determination of the molecularly dominant tumor nodule may be limited by sampling at time of initial diagnosis, may not be present at time of initial diagnosis, or may occur as the disease progresses preventing the development of molecular biomarkers for prostate cancer progression. 281 cases from the population-based Swedish-Watchful Waiting cohort. The cohort consists of men with localized prostate cancer (clinical stage T1-T2, Mx, N0); Training set: first 186 samples; Validation cohort: remaining 95 cases from the same population.

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