High resolution magic angle spinning NMR spectroscopy for metabolic assessment of cancer presence and Gleason score in human prostate needle biopsies

Asten, Jack J.A. van; Cuijpers, Vincent M.J.I.; Kaa, Christina Hulsbergen–van de; Soede‐Huijbregts, C.; Witjes, J. Alfred; Verhofstad, A.A.J.; Heerschap, Arend

doi:10.1007/s10334-008-0156-9

Cited by 65 publications

(80 citation statements)

References 32 publications

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“…Although not the main objective of this study, we present results supporting the inverse correlation between the citrate signal and the Gleason score (6,31,32). In cancer samples with equal amounts of benign epithelium and stroma, we observed lower citrate levels in high-risk samples (Gleason score >8) than in low-risk samples (Gleason score ¼ 6; Fig.…”

Section: Tissue Heterogeneity and Tumor Aggressivity Assessmentsupporting

confidence: 76%

Changes in Gene Transcription Underlying the Aberrant Citrate and Choline Metabolism in Human Prostate Cancer Samples

Bertilsson

Tessem

Flatberg

et al. 2012

Clinical Cancer Research

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Purpose: Low concentrations of citrate and high concentrations of choline-containing compounds (ChoCC) are metabolic characteristics observed by magnetic resonance spectroscopy of prostate cancer tissue. The objective was to investigate the gene expression changes underlying these metabolic aberrations to find regulatory genes with potential for targeted therapies.Experimental design: Fresh frozen samples (n ¼ 133) from 41 patients undergoing radical prostatectomy were included. Histopathologic evaluation was carried out for each sample before a metabolic profile was obtained with high-resolution magic angle spinning (HR-MAS) spectroscopy. Following the HR-MAS, RNA was extracted from the same sample and quality controlled before carrying out microarray gene expression profiling. A partial least square statistical model was used to integrate the data sets to identify genes whose expression show significant covariance with citrate and ChoCC levels.Results: Samples were classified as benign, n ¼ 35; cancer of low grade (Gleason score 6), n ¼ 24; intermediate grade (Gleason score 7), n ¼ 41; or high grade (Gleason score !8), n ¼ 33. RNA quality was high with a mean RNA Integrity Number score of 9.1 (SD 1.2). Gene products predicting significantly a reduced citrate level were acetyl citrate lyase (ACLY, P ¼ 0.003) and m-aconitase (ACON, P < 0.001). The two genes whose expression most closely accompanied the increase in ChoCC were those of phospholipase A2 group VII (PLA2G7, P < 0.001) and choline kinase a (CHKA, P ¼ 0.002).Conclusions: By integrating histologic, transcriptomic, and metabolic data, our study has contributed to an expanded understanding of the mechanisms underlying aberrant citrate and ChoCC levels in prostate cancer.

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Section: Tissue Heterogeneity and Tumor Aggressivity Assessmentsupporting

confidence: 76%

Changes in Gene Transcription Underlying the Aberrant Citrate and Choline Metabolism in Human Prostate Cancer Samples

Bertilsson

Tessem

Flatberg

et al. 2012

Clinical Cancer Research

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“…In particular, it proved to be very powerful for corroborating and complementing noninvasive in vivo magnetic resonance spectroscopy studies by aiding assignment and quantification of the in vivo data, generally characterised by poor resolution and signal-tonoise at clinical magnetic field strengths [10][11][12][13][14]. Moreover, much research work has focused on the metabolic differentiation between tumour and healthy tissues, aiming to find possible biomarkers for the presence and/or grade of different cancers such as breast [15,16], brain [17,18], prostate [19][20][21], cervical [22][23][24], colorectal [25,26], hepatic [27], renal [28,29] and gastric cancer [30].…”

Section: Introductionmentioning

confidence: 98%

Can nuclear magnetic resonance (NMR) spectroscopy reveal different metabolic signatures for lung tumours?

et al. 2010

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This study aims to evaluate the potential of (1)H NMR spectroscopy, combined with multivariate statistics, for discriminating between tumour and non-involved (control) pulmonary parenchyma and for providing biochemical information on different histological types. Paired tissue samples from 24 primary lung tumours were directly analysed by high-resolution magic angle spinning (HRMAS) (1)H NMR spectroscopy (500 MHz), and their spectral profiles subjected to principal component analysis (PCA) and partial least squares regression discriminant analysis (PLS-DA). Tumour and adjacent control parenchyma were clearly discriminated in the PLS-DA model with a high level of sensitivity (95% of tumour samples correctly classified) and 100% specificity (no false positives). The metabolites giving rise to this separation were mainly lactate, glycerophosphocholine, phosphocholine, taurine, reduced glutathione and uridine di-phosphate (elevated in tumours) and glucose, phosphoethanolamine, acetate, lysine, methionine, glycine, myo- and scyllo-inositol (reduced in tumours compared to control tissues). Furthermore, PLS-DA of a sub-set of tumour samples allowed adenocarcinomas to be discriminated from carcinoid tumours and epidermoid carcinomas, highlighting differences in metabolite levels between these histological types, and therefore revealing valuable knowledge on the biochemistry of different types of bronchial-pulmonary carcinomas.

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“…Finally, it is interesting to mention the work of Asten et al in which it is demonstrated that the prostate biopsy tissue is not altered after the analysis by HR-MAS, so it can be used for histological diagnosis [8].…”

Section: Prostatementioning

confidence: 99%

In Vivo Spectroscopy vis-à-vis Ex Vivo Spectroscopy: Pearls and Pitfalls: Imaging Review

Razak¹,

Gupta²,

Meena³

2017

Mol Biol

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Aims and objective: The objective of this communication is to bring the metabolomics by magnetic resonance (high resolution spectroscopy) to the clinical radiologist and compare the spectroscopy in vivo (NMR spectroscopy used in clinical) with the high resolution spectroscopy ex vivo (magic angle spectroscopy, HR -MORE). S and analyzing differences, advantages and limitations of each technique in different tissues. Review of the topic:In vivo spectroscopy that is usually performed in the clinic is a non-invasive technique that can provide important information for the diagnosis and monitoring of different lesions. The most well-known applications of in vivo spectroscopy today are those carried out by localized 1H spectroscopy, monovoxel or multivoxel (spectroscopic image), brain, prostate or breast. There are other modalities, such as the 31 P or 13ºC spectroscopy, but they are much less frequent and are only carried out in a few specialized centres. Without any doubt, the most widespread clinical use is confined to the central nervous system. Conclusion:The in vivo spectroscopy provides important metabolic information for the diagnosis of different pathologies, non-invasively, however, this technique has certain limitations, such as low spectral resolution, that is, the number of metabolites that can be identified/quantified; which results in low diagnostic specificity.Ex vivo spectroscopy, however, has a spectral resolution and sensitivity far superior to in vivo techniques, which allows detecting a large number of metabolites, and therefore greatly improves its diagnostic capacity. However, we must not forget that it is an invasive technique, since it is based on the analysis of pieces of tissue (biopsies, surgical pieces...) and therefore loses its usefulness in those lesions that are impossible to biopsy. In conclusion, each technique has its added value and its limitations and it is the correct use of them and the combination of them with other diagnostic parameters, where their clinical potential resides.

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High resolution magic angle spinning NMR spectroscopy for metabolic assessment of cancer presence and Gleason score in human prostate needle biopsies

Abstract: This preliminary study indicates that HRMAS NMR of routinely obtained PNBs can provide detailed metabolic information of intact prostate tissue with clinical relevance.

Cited by 65 publications

References 32 publications

Changes in Gene Transcription Underlying the Aberrant Citrate and Choline Metabolism in Human Prostate Cancer Samples

Changes in Gene Transcription Underlying the Aberrant Citrate and Choline Metabolism in Human Prostate Cancer Samples

Can nuclear magnetic resonance (NMR) spectroscopy reveal different metabolic signatures for lung tumours?

In Vivo Spectroscopy vis-à-vis Ex Vivo Spectroscopy: Pearls and Pitfalls: Imaging Review

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