Application of metabolomics to prostate cancer

Trock, Bruce J.

doi:10.1016/j.urolonc.2011.08.002

Cited by 110 publications

(127 citation statements)

References 46 publications

Supporting

Mentioning

123

Contrasting

Unclassified

Order By: Relevance

Section: Discussionmentioning

confidence: 99%

“…Since the initial demonstration that sarcosine abundance is associated with prostate cancer aggressiveness, several investigators have worked to determine how best to apply metabolomics in cancer diagnosis and patient management, reviewed in Refs. [41,42].The present study examined over 500 prostate tissue samples from two independent cohorts of patients, using a state of the art metabolomics platform comprised of UHPLC-MS/MS and GC-MS [27,28]. This study identified biochemical correlates of prostate cancer aggressiveness using a combination of surgical and pathological findings, namely Gleason pattern, extracapsular extension, and spread to seminal vesicles and/or lymph nodes.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Metabolomic signatures of aggressive prostate cancer

et al. 2013

View full text Add to dashboard Cite

BACKGROUND. Current diagnostic techniques have increased the detection of prostate cancer; however, these tools inadequately stratify patients to minimize mortality. Recent studies have identified a biochemical signature of prostate cancer metastasis, including increased sarcosine abundance. This study examined the association of tissue metabolites with other clinically significant findings. METHODS. A state of the art metabolomics platform analyzed prostatectomy tissues (331 prostate tumor, 178 cancer-free prostate tissues) from two independent sites. Biochemicals were analyzed by gas chromatography-mass spectrometry and ultrahigh performance liquid chromatography-tandem mass spectrometry. Statistical analyses identified metabolites associated with cancer aggressiveness: Gleason score, extracapsular extension, and seminal vesicle and lymph node involvement. RESULTS. Prostate tumors had significantly altered metabolite profiles compared to cancerfree prostate tissues, including biochemicals associated with cell growth, energetics, stress, and loss of prostate-specific biochemistry. Many metabolites were further associated with clinical findings of aggressive disease. Aggressiveness-associated metabolites stratified prostate tumor tissues with high abundances of compounds associated with normal prostate function (e.g., citrate and polyamines) from more clinically advanced prostate tumors. These aggressive prostate tumors were further subdivided by abundance profiles of metabolites including NADþ and kynurenine. When added to multiparametric nomograms, metabolites improved prediction of organ confinement (AUROC from 0.53 to 0.62) and 5-year recurrence (AUROC from 0.53 to 0.64). CONCLUSIONS. These findings support and extend earlier metabolomic studies in prostate cancer and studies where metabolic enzymes have been associated with carcinogenesis and/or outcome. Furthermore, these data suggest that panels of analytes may be valuable to translate metabolomic findings to clinically useful diagnostic tests. Prostate 73: [1547][1548][1549][1550][1551][1552][1553][1554][1555][1556][1557][1558][1559][1560] 2013. KEY WORDS:clinical heterogeneity; prostate cancer; metabolomics; diagnosis INTRODUCTIONProstate cancer is the most common male malignancy with an estimated 240,000 new cases and more than 28,000 deaths in the United States in 2012 [1]. Clinical detection of prostate cancer increased following the widespread adoption of serum prostate-specific antigen (PSA) screening; however, a significant fraction of prostate cancers detected solely on the basis of an increased serum PSA are indolent. As a result of concerns of over-diagnosis and over-treatment, a new paradigm of active surveillance in patient management has emerged recently [2]. The resulting broad spectrum of treatment options (none, focal therapy, radical surgery, or radiation) has been developed in response to the increased detection of low-risk prostate cancer [3]; however, the current panel of diagnostic tests provides limited information regarding the pr...

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Metabolomic signatures of aggressive prostate cancer

et al. 2013

View full text Add to dashboard Cite

show abstract

“…However, efforts at profiling the entire measured metabolome rather than focusing on individual metabolites have been increased 101 . Thus, a more complete depiction of the metabolic alterations among the development of cancer cells could be achieved 102,103,104,105 .…”

Section: Metabolomic Imaging -Results Of a Preliminary Studymentioning

confidence: 99%

Metabolomic Imaging for Human Prostate Cancer Detection using MR Spectroscopy at 7-T

Langhammer¹,

Cheng²,

Nowak³

et al. 2014

Fortschr Röntgenstr

View full text Add to dashboard Cite

BACKGROUND. Prostate cancer (PCa) remains a major health concern in men of the Western World. However, we still lack effective diagnostic tools a) for an effective screening with both high sensitivity and specificity, b) to guide biopsies and avoid histology sampling errors and c) to predict tumor aggressiveness in order to avoid overtreatment. Therefore, a more reliable, highly cancer-specific and ideally in vivo approach is needed. The present study has been designed in order to further develop and test the method of "metabolomic imaging" using magnetic resonance spectroscopy (MRS) at 7T to address those challenges. METHODS.Thirty whole prostates with biopsy-proven PCa were in vitro analyzed with a 7T human MR scanner. A voxel grid containing the spectral information was overlaid with the MR image of the middle transverse cross-sectional plane of each case. Subsequent histopathological evaluation of the prostate specimen followed. After the spectral output was processed, all voxels were compared with a metabolomic PCa profile, which had been established within a preliminary study, in order to create a metabolomic map indicating MRS cancer-suspicious regions. Those regions were compared with the histologically identified tumor lesions regarding location. RESULTS. CONCLUSION.A new approach within PCa diagnostics was developed with spectral analysis including the whole measureable metabolome -referred to as "metabolomics" -rather than focusing on single metabolites. The MI facilitates precise tumor detection and may additionally serve as a marker for tumor aggressiveness. Metabolomic imaging might contribute to a highly cancer-specific in vivo diagnostic protocol for PCa.

show abstract

“…When nuclei in a magnetic field are exposed to a radiofrequency pulse their protons temporarily move to a higher energy state, and then release a characteristic radiowave when they return to their normal energy state [75]. The resulting NMR spectrum is a collection of characteristic peaks and intensities of each compound that allow its identification [76].…”

Section: Nuclear Magnetic Resonancementioning

confidence: 99%