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

Abstract

Prostate cancer (PCa) is the most frequently diagnosed cancer and the second leading cause of cancer death among men in Western countries. Current screening techniques are based on the measurement of serum prostate specific antigen (PSA) levels and digital rectal examination. A decisive diagnosis of PCa is based on prostate biopsies; however, this approach can lead to false-positive and false-negative results. Therefore, it is important to discover new biomarkers for the diagnosis of PCa, preferably noninvasive ones. Metabolomics is an approach that allows the analysis of the entire metabolic profile of a biological system. As neoplastic cells have a unique metabolic phenotype related to cancer development and progression, the identification of dysfunctional metabolic pathways using metabolomics can be used to discover cancer biomarkers and therapeutic targets. In this study, we review several metabolomics studies performed in prostatic fluid, blood plasma/serum, urine, tissues and immortalized cultured cell lines with the objective of discovering alterations in the metabolic phenotype of PCa and thus discovering new biomarkers for the diagnosis of PCa. Encouraging results using metabolomics have been reported for PCa, with sarcosine being one of the most promising biomarkers identified to date. However, the use of sarcosine as a PCa biomarker in the clinic remains a controversial issue within the scientific community. Beyond sarcosine, other metabolites are considered to be biomarkers for PCa, but they still need clinical validation. Despite the lack of metabolomics biomarkers reaching clinical practice, metabolomics proved to be a powerful tool in the discovery of new biomarkers for PCa detection.

Metabolic alterations in urine extracellular vesicles are associated to prostate cancer pathogenesis and progression

“…The urine level of this metabolite was increased in men with metastatic PCa [44]. However, its utility as a potential diagnostic tool is unclear, as its validation as a biomarker has failed in several studies (reviewed in [11,45]). Interestingly, we have detected sarcosine in urinary EVs, and although not significant ( p =  0.09), its level was decreased in PCa samples.…”

Metabolomics and transcriptomics profiles reveal the dysregulation of the tricarboxylic acid cycle and related mechanisms in prostate cancer

“…5 One of the most important metabolic characteristics in PCa is an increased citrate oxidation because of the inability of the epithelial cells to accumulate zinc. 6 Acetyl-coenzyme A (acetyl-CoA) is essential for citrate synthesis. [6][7][8] This transformation from citrate accumulation in normal epithelial cells to the citrate oxidation in prostate cancer cells may benefit to provide more efficient energy production.…”

“…[6][7][8] This transformation from citrate accumulation in normal epithelial cells to the citrate oxidation in prostate cancer cells may benefit to provide more efficient energy production. 6,9 In addition, due to the augmentation of membrane synthesis in malignant cells, phosphocholine, total choline containing compounds and creatine levels are elevated in PCa compared to normal tissues. Increased uptake of fatty acids 9 and overexpression of enzymes involved in b-oxidation 10 were observed in prostate tumors, which can provide ATP and acetyl-CoA to main accelerated citrate oxidation.…”

Cancer-Devoted Liquid Biopsies and Applications to Prostate Cancer

“…Unique among the selected papers, Lima et al [24] performed an update in metabolomics studies of biomarkers in prostatic fluid, blood, plasma/serum, urine, tissues for human PCa. Sarcosine, one of the most promising biomarkers identified to date remains a controversial issue in the clinic.…”