Seminal plasma metabolomics reveals lysine and serine dysregulation as unique features distinguishing between prostate cancer tumors of Gleason grades 6 and 7

Abstract

Background: Prostate cancer (PCa) is a metabolic disease. Most men are diagnosed with low grade indolent disease and differentiating these men from those who have life threatening cancer is a challenging but important clinical dilemma. There are currently limited biomarkers that can distinguish between the indolent Gleason grade 6 and higher-grade disease. Moreover, some individuals initially diagnosed with low grade disease progress to higher grade disease. Currently prostate biopsies are the only reliable methods of stratifying risk, but biopsies can cause significant morbidity, sample only a small portion of the gland and are costly. Therefore, biomarkers distinguishing between indolent and aggressive patterns of PCa are urgently required to minimize biopsy-associated morbidity, prevent over-treatment of indolent PCa and to better stratify patients for appropriate treatment.

Methods: Seminal fluid samples were collected from normal individuals (n = 13) Before infertility treatment and histologically confirmed PCa patients (n = 51). ¹ H Nuclear magnetic resonance spectroscopy and orthogonal partial least square discriminant analysis were used to compare the populations.

Results: Alterations in amino acids levels, specifically lysine and serine and changes in glycolytic intermediates were the most significant metabolic features associated with differences between healthy controls and PCa and between Gleason grade 6 (GS6) and Gleason grade 7 (GS7) samples. Orthogonal partial least square plots discriminated healthy controls from PCa samples (R ² = 0.54, Q ² = 0.31; area under the receiver operating characteristics curve [AUC] = 0.96), and GS6 from GS7 samples (R ² = 0.62, Q ² = 0.49; AUC = 0.98) based on lysine and serine content.

Conclusion: This study suggests that seminal plasma metabolomics profiling of seminal fluid is a promising means of differentiating indolent from aggressive disease. Particularly, lysine and serine levels may be able to differentiate GS6 from GS7 disease.

Keywords: Gleason score; amino acids; metabolic profiling; semen.