Recent Advances in Metabolic Profiling and Imaging of Prostate Cancer

Abstract

Cancer is a metabolic disease. Cancer cells, being highly proliferative, show significant alterations in metabolic pathways such as glycolysis, respiration, the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, lipid metabolism, and amino acid metabolism. Metabolites like peptides, nucleotides, products of glycolysis, the TCA cycle, fatty acids, and steroids can be an important read out of disease when characterized in biological samples such as tissues and body fluids like urine, serum, etc. The cancer metabolome has been studied since the 1960s by analytical techniques such as mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. Current research is focused on the identification and validation of biomarkers in the cancer metabolome that can stratify high-risk patients and distinguish between benign and advanced metastatic forms of the disease. In this review, we discuss the current state of prostate cancer metabolomics, the biomarkers that show promise in distinguishing indolent from aggressive forms of the disease, the strengths and limitations of the analytical techniques being employed, and future applications of metabolomics in diagnostic imaging and personalized medicine of prostate cancer.

Metabonomic analysis of metastatic lung tissue in breast cancer mice by an integrated NMR-based metabonomics approach

“…27 Therefore, the increased alanine possibly suggested the activated transamination, which was also found in prostate cancer and head and neck cancer. 37,38 Valine, one of the branched-chain amino acids, was downregulated in both models at serious lung metastatic stage. In human lung cancer, valine is also signicantly decreased, 39 which may be a result from disordered activity of a series of synthases during the tumor growth.…”

Nuclear magnetic resonance spectroscopy as a new approach for improvement of early diagnosis and risk stratification of prostate cancer

“…To date only a few studies have used nuclear magnetic resonance (NMR) to define metabolomic signatures of PCa for diagnosis and risk assessment (Kumar et al, 2016a), while most studies used liquid chromatography-mass spectrometry (LC-MS) or capillary electrophoresis-mass spectrometry (CE-MS) (Roberts et al, 2011;McDunn et al, 2013;Thapar and Titus, 2014;Struck-Lewicka et al, 2015).…”

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

“…Cancer cells are highly proliferative and show specific alterations in metabolic pathways that can be detected using MRS 59,62 . In PCa research, the most commonly applied metabolite markers are citrate and choline.…”

“…Among solid samples, however, molecules experience anisotropic effects, causing spectral line broadening and therefore low resolution, hindering the distinction of individual metabolites. In consequence, MRS of solid tissue was of limited use, whereas conventional MRS using aqueous solutions did not allow subsequent histopathological evaluation 72,75,76 59,72 .…”

“…Initially, single metabolites or metabolite ratios were analyzed in order to reveal the molecular changes in cell metabolism of PCa cells 59,88,89,90 . In particular the ratio of (choline+creatine)/citrate, shortly (C+C)/C, seems to have a strong potential to improve accuracy in PCa detection 91,92,93 Gleason score of 3+3 were detected with a sensitivity of 44%, whereas for Gleason scores of 4+3 and higher, detection rates of over 85% were achieved 100 .…”