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1H HRMAS NMR Derived Bio-markers Related to Tumor Grade, Tumor Cell Fraction, and Cell Proliferation in Prostate Tissue Samples
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
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2011 (English)In: Biomarker Insights, ISSN 1177-2719, Vol. 6, 39-47 p.Article in journal (Refereed) Published
Abstract [en]

A high-resolution magic angle spinning NMR spectroscopic approach is presented for evaluating the occurrence, amount and aggressiveness of cancer in human prostate tissue samples. Using this technique, key metabolites in malignant and non-malignant samples (n = 149) were identified, and patterns of their relative abundance were analyzed by multivariate statistical methods. Ratios of various metabolites – including (glycerophophorylcholine + phosphorylcholine)/creatine, myo-inositol/scyllo-inositol, scyllo-inositol/creatine, choline/creatine, and citrate/creatine – correlated with: i) for non-malignant tissue samples, the distance to the nearest tumor and its Gleason score and; ii) the fraction of tumor cells present in the sample; and iii) tumor cell proliferation (Ki67 labelling index). This NMR-based approach allows the extraction of information that could be useful for developing novel diagnostic methods for prostate cancer.

Place, publisher, year, edition, pages
Libertas Academica Ltd , 2011. Vol. 6, 39-47 p.
Keyword [en]
prostate cancer, HRMAS, MRSI, inositol, Gleason score, Ki67
National Category
Cancer and Oncology
URN: urn:nbn:se:umu:diva-41205DOI: 10.4137/BMI.S6794OAI: diva2:405031
Available from: 2011-03-21 Created: 2011-03-21 Last updated: 2011-09-27Bibliographically approved
In thesis
1. Prostate Cancer Diagnosis: experimental and Clinical Studies With HRMAS NMR Spectroscopy
Open this publication in new window or tab >>Prostate Cancer Diagnosis: experimental and Clinical Studies With HRMAS NMR Spectroscopy
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A few abnormal cells found in a small piece of prostate tissue are most consequential for a man’s future.

The prevalence of prostate cancer (PCa) is increasing globally. The main instigating factor for this cancer is not yet known, but it appears to be the consequence of many variables such as an increasingly older population, more frequent PSA-testing, and factors involving lifestyle.

Prostate cancer screening, as an equivalent for breast cancer screening, has been suggested but unfortunately there are no accurate diagnostic tools available for this type of screening. The reason for this is simply that the prostate is one of the most difficult organs to diagnose and, consequently, PCa screening would generate far too many false-positive and false-negative results.  The prostate is not easily accessible as it is deeply-seated in the male pelvic area, wrapped around the urethra and surrounded by sensitive vital organs.  Furthermore, PCa is frequently multi-focal, and the cancer cells have a tendency of assimilating among normal cells and, thus, do not always form solid lumps.  Therefore, prostate tumors are often not felt by digital rectal examination (DRE) or identified by imaging.  The PSA-test is not reliable as it is more prostate-specific than cancer-specific.  Due to increasing prostate awareness, more early-stage and locally confined PCa are being detected. This is saving lives, although there is a high risk of over treatment and unnecessary side-effects.  The increased detection of PCa requires sophisticated diagnostic methods and highly skilled clinicians who can discern between indolent and aggressive cancers.  The current “gold-standard” for PCa diagnosis is biopsy grading by pathologists using the Gleason score system, which is a difficult task.  Therefore, innovative methods to improve the precision of prostate diagnosis, by increased biopsy sensitivity and tumor localization, are of essence.

In light of these difficulties, the metabolomic approach using 1D and 2D high-resolution magic angle spinning (HRMAS) NMR spectroscopy combined with histopathology on intact prostatectomy specimens was evaluated in this research project.  The non-destructive nature of HRMAS NMR enables spectroscopic analysis of intact tissue samples with consecutive histological examinations under light microscope. Metabolomics aids in the unraveling and the discovery of organ-specific endogenous metabolites that have the potential to be reliable indicators of organ function and viability, extrinsic and intrinsic perturbations, as well as valuable markers for treatment response. The results may, therefore, be applied clinically to characterize an organ by utilizing biomarkers that have the capacity to distinguish between disease and health.

The aim was to characterize the human and the rat prostate in terms of its intermediary metabolism, which I show here to differ between species and anatomical regions.  Furthermore, the aim is to seek the verification of HRMAS NMR derived metabolites which are known to be a part of the prostate metabolome such as, citrate, choline, and the polyamines which were performed, but also the identification of metabolites not previously identified as part of the local prostate metabolism, such as Omega-6, which was detected in tumors.  The extended aim was to elucidate novel bio-markers with clinical potential. In this study, the common phyto-nutrient, inositol, which appears to possess protective properties, was identified as being a potentially important PCa bio-marker for the distinction between the more indolent Gleason score 6 and the more aggressive Gleason score 7 in non-malignant prostate tissues with tumors elsewhere in the organ. Further studies in this area of PCa research are therefore warranted.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2011. 80 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1406
Prostate cancer, PCa, HRMAS NMR, MRSI, metabolomics, Gleason score, citrate, inositol, choline, Krebs cycle, PUFA, omega-6, omega-3
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
urn:nbn:se:umu:diva-43651 (URN)978-91-7459-154-5 (ISBN)
Public defence
2011-05-27, Sal 260, byggnad 3A, plan 2, Norrlands universitetssjukhus, Umeå, 13:00 (Swedish)
Available from: 2011-05-06 Created: 2011-05-05 Last updated: 2011-05-06Bibliographically approved

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Stenman, KatarinaStattin, PärStenlund, HansRiklund, KatrineGröbner, GerhardBergh, Anders
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