Change search
ReferencesLink to record
Permanent link

Direct link
Two-dimensional difference gel electrophoresis to reveal proteins in plasma associated with high risk prostate cancer
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Show others and affiliations
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Prostate cancer is a common but highly variable disease. Conventional methods for prognostication are limited and needed to be complemented by novel biomarkers which could identify clinically significant tumors at a curable timepoint. With the aim to find biomarkers in plasma for high risk prostate cancer, we combined the ProteoMiner technology for protein fractionation with 2-dimentional difference gel electrophoresis (2D-DIGE). Plasma samples from patients with high risk tumors, defined to have bone metastases (M1, N=7) or locally advanced or poorly differentiated prostate cancer (M0, N=14), or benign disease (N=15) were analyzed. As a result of combined univariate and multivariate analyses (orthogonal partial least-squares discriminant analysis, OPLS-DA), 338 protein spots were found to be significantly associated with high risk prostate cancer. Ninety-eight (98) of the spots were successfully identified by LC-MS/MS, and OPLS-DA of those resulted in a reliable method for class separation; M1 vs. M0 vs. B (R2Xcum: 31.1%, R2Y cum: 59.9%, Q2cum: 41.4%, P < 0.0001). The panel of identified potential protein markers for high risk prostate cancer included highly to intermediately abundant plasma proteins involved in key processes such as lipid transport, coagulation, inflammation, and immune responses. Their putative roles for prostate cancer progression are discussed.

Keyword [en]
biomarkers, 2D-DIGE, plasma, prostate cancer, proteomics, PorteoMiner
URN: urn:nbn:se:umu:diva-43511OAI: diva2:414380
Available from: 2011-05-03 Created: 2011-05-03 Last updated: 2011-05-04Bibliographically approved
In thesis
1. Proteomics and metabolomics in biological and medical applications
Open this publication in new window or tab >>Proteomics and metabolomics in biological and medical applications
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Biological processes in living organisms consist of a vast number of different molecular networks and interactions, which are complex and often hidden from our understanding. This work is focused on recovery of such details for two quite distant examples: acclimation to extreme freezing tolerance in Siberian spruce (Picea obovata) and detection of proteins associated with prostate cancer.

The first biological system in the study, upon P. obovata, is interesting by this species ability to adapt and sustain extremely low temperatures, such as -60⁰C or below. Despite decades of investigations, the essential features and mechanisms of the amazing ability of this species still remains unclear. To enhance knowledge about extreme freezing tolerance, the metabolome and proteome of P. obovata’s needles were collected during the tree’s acclimation period, ranging from mid August to January, and have been analyzed.

The second system within this study is the plasma proteome analysis of high risk prostate cancer (PCa) patients, with and without bone metastases. PCa is one of the most common cancers among Swedish men, which can abruptly develop into an aggressive, lethal disease. The diagnostic tools, including PSA-tests, are insufficient in predicting the disease’s aggressiveness and novel prognostic markers are urgently required.

Both biological systems have been analyzed following similar steps: by two-dimensional difference gel electrophoresis (2D-DIGE) techniques, followed by protein identification using mass spectrometry (MS) analysis and multivariate methods. Data processing has been utilized for searching for proteins that serve as unique indicators for characterizing the status of the systems. In addition, the gas chromatography-mass spectrometry (GC-MS) study of the metabolic content of P.obovata’s needles, from the extended observation period, has been performed. The studies of both systems, combined with thorough statistical analysis of experimental outcomes, have resulted in novel insights and features for both P. obovata and prostate cancer. In particular, it has been shown that dehydrins, Hsp70s, AAA+ ATPases, lipocalin and several proteins involved in cellular metabolism etc., can be uniquely associated with acclimation to extreme freezing in conifers. Metabolomic analysis of P. obovata needles has revealed systematic metabolic changes in carbohydrate and lipid metabolism. Substantial increase of raffinose, accumulation of desaturated fatty acids, sugar acids, sugar alcohols, amino acids and polyamines that may act as compatible solutes or cryoprotectants have all been observed during the acclimation process.

Relevant proteins for prostate cancer progression and aggressiveness have been identified in the plasma proteome study, for patients with and without bone metastasis. Proteins associated with lipid transport, coagulation, inflammation and immune response have been found among them. 

Place, publisher, year, edition, pages
Umeå: Kemiska institutionen, Umeå Universitet, 2011. 44 p.
2D-DIGE, biomarkers, cold-acclimation, conifer, freezing tolerance, GC-MS, metabolomics, multiple hypothesis test, multivariate analysis, OPLS-DA, Picea obovata, plasma, prostate cancer, proteomics, ProteoMiner, Siberian spruce
National Category
Chemical Sciences
urn:nbn:se:umu:diva-43520 (URN)978-91-7459-204-7 (ISBN)
Public defence
2011-05-25, KBC-huset, KB3A9, Umeå Universitet, Umeå, 10:00 (English)
Available from: 2011-05-04 Created: 2011-05-03 Last updated: 2014-12-10Bibliographically approved

Open Access in DiVA

No full text

Search in DiVA

By author/editor
Shiryaeva, LiudmilaAntti, HenrikStattin, PärKieselbach, ThomasSchröder, Wolfgang P.Wikström, Pernilla
By organisation
Department of ChemistryUrology and AndrologyPathology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 60 hits
ReferencesLink to record
Permanent link

Direct link