Metabolomic profiling for the identification of novel diagnostic markers in prostate cancer

Abstract

Metabolomic profiling offers a powerful methodology for understanding the perturbations of biochemical systems occurring during a disease process. During neoplastic transformation, prostate cells undergo metabolic reprogramming to satisfy the demands of growth and proliferation. An early event in prostate cell transformation is the loss of capacity to accumulate zinc. This change is associated with a higher energy efficiency and increased lipid biosynthesis for cellular proliferation, membrane formation and cell signaling. Moreover, recent studies have shown that sarcosine, an N-methyl derivative of glycine, was significantly increased during disease progression from normal to localized to metastatic prostate cancer. Mapping the metabolomic profiles to their respective biochemical pathways showed an upregulation of androgen-induced protein synthesis, an increased amino acid metabolism and a perturbation of nitrogen breakdown pathways, along with high total choline-containing compounds and phosphocholine levels. In this review, the role of emerging biomarkers is summarized, based on the current understanding of the prostate cancer metabolome.

Biomarker Discovery in Human Prostate Cancer: an Update in Metabolomics Studies

“…The observation that the glutamine transporter and glutaminase are both overexpressed in PCa cells was proof of the importance of this mechanism in PCa [38], [39], [40]. The α-ketoglutarate derivate from glutamine can contribute to the formation of citrate when incorporated into the Krebs cycle (oxidation pathway); however, α-ketoglutarate can also be transformed into citrate by the reversal of the tricarboxylic acid cycle through reductive carboxylation.…”

“…Sterol regulatory element-binding protein–1, an essential transcription factor for lipogenesis, is also implicated in AR transcriptional regulation. Beyond increased lipogenesis, sterol regulatory element-binding protein–1 also increased reactive oxygen species production and the expression of NADPH oxidase, which leads to proliferation, migration, and invasion of PCa cells [36], [37], [38]. In PCa cells, the levels of choline and creatine are increased because there is an augmentation of membrane synthesis for cell proliferation [16].…”

“…Cancer-associated fibroblasts in the myofibroblastic microenvironment undergo the Warburg effect, induced by epithelial cancer cells, and secrete lactate and pyruvate. The lactate and pyruvate are taken up by the PCa cells and used for the Krebs cycle, anabolic metabolism, and cell proliferation [38], [42], [43].…”

Biomarkers in Localized Prostate Cancer

“…This approach can be used to characterize the metabolic fingerprint of a tumor and identify novel markers that may be used for prostate cancer early detection, prognostic stratification and therapy response monitoring [54].…”

Vitamins, metabolomics, and prostate cancer

“…Metabolomics platforms or laboratory assays used for biospecimen analysis vary substantially and include NMR, high performance liquid chromatography (HPLC), MS in tandem with either liquid or gas chromatography (LC/MS or GC/MS), and enzyme-linked immunosorbent assay (ELISA) [91]. Metabolite limits of detection and sensitivity vary by analytical method, and sample preparation differences can introduce substantial variation in observed metabolite concentrations [91]. A wide variety of biological samples have been profiled for prostate cancer cases with diverse clinical and histopathological characteristics (e.g., stage and Gleason), including tissue from biopsies, radical prostatectomies, and distant metastases.…”