³¹P NMR of phospholipid metabolites in prostate cancer and benign prostatic hyperplasia

Abstract

1 H MRSI in vivo is increasingly being used to diagnose prostate cancer noninvasively by measurement of the resonance from choline-containing phospholipid metabolites. Although 31 P NMR in vivo or in vitro is potentially an excellent method for probing the phospholipid metabolites prominent in prostate cancer, it has been little used recently. Here, we report an in vitro 31 P NMR comparison of prostate cancer and benign prostatic hyperplasia, focusing on the levels of the major phospholipid metabolites. Unlike phosphocholine and glycerophosphocholine, phosphoethanolamine and glycerophosphoethanolamine (and their ratio) were significantly different between cancer and benign prostatic hyperplasia. The high level of phosphoethanolamine1glycerophosphoethanolamine relative to phosphocholine1glycerophosphocholine suggests that the former may be significant contributors to the ''total choline'' resonance observed by

31P MR spectroscopic imaging of the human prostate at 7 T: T1relaxation times, Nuclear Overhauser Effect, and spectral characterization

“…This contrasts with the 1 H HR-MAS spectra, which showed clear signal of the phosphodiesters, whereas PC was nearly undetectable. The ratio between PE and PC observed in vivo differed from in vitro observations, in which PE was more abundant than PC, especially in the 1 H HR-MAS spectra (%6Â in 31 P highresolution NMR spectra; 30-250Â in 1 H HR-MAS spectra) (7,(41)(42)(43). The differences between in vivo and in vitro results suggest metabolite content changes during extraction and in vitro measurements.…”

“…The near absence of GPE and GPC in the in vivo spectra was also noticed in 31 P highresolution NMR spectra of perchloric extracts of prostate tissue (41,42). This contrasts with the 1 H HR-MAS spectra, which showed clear signal of the phosphodiesters, whereas PC was nearly undetectable.…”

Metabolomic Biomarkers of Prostate Cancer: Prediction, Diagnosis, Progression, Prognosis, and Recurrence

“…Steroid hormones (23) which help regulate the growth and function of the prostate were also implicated (62), as were inositol and its isomers (27) which are involved in osmoregulation, and have been shown to be dysregulated in several other cancers(55) and cortisol (35) which is thought to be related to cancer development via the mechanism of chronic stress (63). A number of these metabolites; citrate, inositol, lactate (25) and cortisol (35, 63), were additionally observed to differ between BHP and prostate cancer patients, along with phosphoethanolamine, and glycerophosphoethanolamine (29) which are also components of membranes and acetate (25) which is thought to support cell proliferation through de novo lipid biosynthesis (64). …”

“…In common with the majority of the existing metabolomics literature (54), all studies were case-control in design; including two nested within cohorts (22, 23). Twenty-two studies used external controls who were either healthy (n=13 studies) (22, 23, 34, 37-42, 49-52), suffering from benign prostatic hyperplasia (BPH) (n=3) (26, 29, 53), non-recurrent cases (n=2) (45, 48) or they included multiple control groups (n=4) (25, 35, 36, 43). In the remainder, the prostate cancer cases acted as their own controls through the use of matched biological samples or the measurement of metabolites pre-and post-therapy.…”

“…Seventeen studies took an untargeted approach to the search for discriminatory metabolites, with only 12 employing a targeted search. The targeted approach introduces an inherent bias as it is only able to detect the specific metabolites or metabolite classes, such as methionine metabolites (48), corticoids (35), or lipids (29, 40), which have been previously determined. However, it should be noted that the quantitative nature of the targeted studies offers the distinct advantage of easier translation into a clinical setting.…”