Advances and Perspectives in Prostate Cancer Biomarker Discovery in the Last 5 Years through Tissue and Urine Metabolomics

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.

Keywords: biomarkers; lipidomics; metabolic pathways; metabolomics; prostate cancer; tissue; urine; volatilomics.

Figure 1

Schematic representation of the metabolic phenotype of prostate cancer cells. Red indicates increase in either metabolites or metabolic pathway flux and green indicates decrease in either metabolites or metabolic pathway flux. Underline indicates changes especially important in advanced PCa. The dashed lines represent multiple steps reactions. (α-KG, alpha-ketoglutarate; Ac-CoA, acetyl-coenzyme A; Chol, choline; G6P, glucose-6-phosphate; GNMT, glycine N-methyltransferase; Isocit, isocitrate; Met, methionine; NO, nitric oxide; OAA, oxaloacetate; PCs, phosphatidylcholines; PEs, phosphatidylethanolamines; PPP, pentose phosphate pathway; R5P, ribose-5-phosphate; SAH, S-adenosylhomocysteine; SAM, S-adenosylmethionine; SARDH, sarcosine dehydrogenase; TCA cycle, tricarboxylic acid cycle).

Figure 2

Metabolites referred with the same variation in more than one study performed in PCa tissue in the last 5 years. The black bars represent metabolites increased in PCa and the grey bars represent metabolites decreased in PCa.

Figure 3

Metabolites found with the same alteration in urine metabolome of PCa patients in more than one study, in the last 5 years. The black bars represent metabolites increased in PCa and the grey bars represent metabolites decreased in PCa. The listed bars correspond to the metabolites that were previously found with the same variation in PCa tissue.