Abstract
Prostate cancer (PCa) is the second most diagnosed cancer in men worldwide. For its screening, serum prostate specific antigen (PSA) test has been largely performed over the past decade, despite its lack of accuracy and inability to distinguish indolent from aggressive disease. Metabolomics has been widely applied in cancer biomarker discovery due to the well-known metabolic reprogramming characteristic of cancer cells. Most of the metabolomic studies have reported alterations in urine of PCa patients due its noninvasive collection, but the analysis of prostate tissue metabolome is an ideal approach to disclose specific modifications in PCa development. This review aims to summarize and discuss the most recent findings from tissue and urine metabolomic studies applied to PCa biomarker discovery. Eighteen metabolites were found consistently altered in PCa tissue among different studies, including alanine, arginine, uracil, glutamate, fumarate, and citrate. Urine metabolomic studies also showed consistency in the dysregulation of 15 metabolites and, interestingly, alterations in the levels of valine, taurine, leucine and citrate were found in common between urine and tissue studies. These findings unveil that the impact of PCa development in human metabolome may offer a promising strategy to find novel biomarkers for PCa diagnosis.
Highlights
Cancer diseases are one of the most important health problems worldwide, prostate cancer (PCa) being one of the most prevalent
PCa screening is based in serum prostate specific antigen (PSA) test and digital rectal examination (DRE) [4], whereas prostate biopsy (PB) is mandatory for a final diagnosis [5]
High levels of PSA (>4 ng/mL) are considered a sign of PCa [4]. This biomarker shows important limitations [6], due to its reduced accuracy (62–75%) [7], sensitivity (20.5%), specificity [4,8], and area under the curve (AUC) [7]. These low performance values can be due to interference from other diseases, like benign prostate hyperplasia (BPH) or prostatitis, that may lead to an increase in serum PSA levels [2,6]
Summary
Cancer diseases are one of the most important health problems worldwide, prostate cancer (PCa) being one of the most prevalent. Considering the limitations of the currently available PCa diagnostic tools, the scientific community has performed massive efforts to discover new biomarkers for PCa detection These biomarkers include several derivatives of PSA, like the prostate health index (PHI) and the 4Kscore tests. Prostarix test, which is performed in urine after DRE, was developed using metabolomic approaches and detects four amino acids [17], namely sarcosine, glycine, alanine, and glutamate [13,16] This test has not yet obtained FDA approval [13], but it is commercially available and is recommended for men with persistent PSA increase and previously negative PB [13,17]. A total of 25 studies were included, of which 12 were performed in PCa tissue samples, 12 in PCa urine samples and one study included both matrices
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