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Original Article | Open Access

A novel expressed prostatic secretion (EPS)-urine metabolomic signature for the diagnosis of clinically significant prostate cancer

Denise Drago1,*Annapaola Andolfo1,* ( )Ettore Mosca2Alessandro Orro2Luigi Nocera3Vito Cucchiara3Matteo Bellone4Francesco Montorsi3Alberto Briganti3
ProMeFa, Proteomics and Metabolomics Facility, Center for Omics Sciences (COSR), IRCCS San Raffaele Scientific Institute, Milan 20132, Italy
Institute of Biomedical Technologies, National Research Council (CNR), Milan 20090, Italy
Department of Urology and Division of Experimental Oncology, Urological Research Institute (URI), IRCCS San Raffaele Scientific Institute, Milan 20132, Italy
Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy

*These authors contributed equally to this work.

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Abstract

Objective

Significant efforts are currently being made to identify novel biomarkers for the diagnosis and risk stratification of prostate cancer (PCa). Metabolomics can be a very useful approach in biomarker discovery because metabolites are an important read-out of the disease when characterized in biological samples. We aimed to determine a metabolomic signature which can accurately distinguish men with clinically significant PCa from those affected by benign prostatic hyperplasia (BPH).

Methods

We first performed untargeted metabolomics using ultrahigh-performance liquid chromatography tandem mass spectrometry on expressed prostatic secretion urine (EPS-urine) from 25 patients affected by BPH and 25 men with clinically significant PCa (defined as Gleason score ≥ 3 + 4). Diagnosis was histologically confirmed after surgical treatment. The EPS-urine metabolomic approach was then applied to a larger, prospective cohort of 92 consecutive patients undergoing multiparametric magnetic resonance imaging for clinical suspicion of PCa prior to biopsy.

Results

We established a novel metabolomic signature capable of accurately distinguishing PCa from benign tissue. A metabolomic signature was associated with clinically significant PCa in all subgroups of the Prostate Imaging Reporting and Data System (PI-RADS) classification (100% and 89.13% of accuracy when the PI-RADS was in range of 1–2 and 4–5, respectively, and 87.50% in the more critical cases when the PI-RADS was 3).

Conclusions

A combination of metabolites and clinical variables can effectively help in identifying PCa patients that might be overlooked by current imaging technologies. Metabolites from EPS-urine should help in defining the diagnostic pathway of PCa, thus improving PCa detection and decreasing the number of unnecessary prostate biopsies.

References

1

Cooperberg MR, Carroll PR, Klotz L. Active surveillance for prostate cancer: progress and promise. J Clin Oncol. 2011; 29: 3669-76.

2

Cucchiara V, Cooperberg MR, Dall’Era M, Lin DW, Montorsi F, Schalken JA, et al. Genomic markers in prostate cancer decision making. Eur Urol. 2018; 73: 572-82.

3

Ahmed HU, El-Shater Bosaily A, Brown LC, Gabe R, Kaplan R, Parmar MK, et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet. 2017; 389: 815-22.

4

Lucarelli G, Loizzo D, Ferro M, Rutigliano M, Vartolomei MD, Cantiello F, et al. Metabolomic profiling for the identification of novel diagnostic markers and therapeutic targets in prostate cancer: an update. Expert Rev Mol Diagn. 2019; 19: 377-87.

5

Trock BJ. Application of metabolomics to prostate cancer. Urol Oncol. 2011; 29: 572-81.

6

Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, et al. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009; 457: 910-4.

7

Swindle P, McCredie S, Russell P, Himmelreich U, Khadra M, Lean C, et al. Pathologic characterization of human prostate tissue with proton MR spectroscopy. Radiology. 2003; 228: 144-51.

8

Gulley JL, Emberton M, Kurhanewicz J, Choyke P. Progress in prostate cancer imaging. Urol Oncol. 2012; 30: 938-9.

9

Kurhanewicz J, Vigneron DB, Brindle K, Chekmenev EY, Comment A, Cunningham CH, et al. Analysis of cancer metabolism by imaging hyperpolarized nuclei: prospects for translation to clinical research. Neoplasia. 2011; 13: 81-97.

10

Nelson SJ, Kurhanewicz J, Vigneron DB, Larson PE, Harzstark AL, Ferrone M, et al. Metabolic imaging of patients with prostate cancer using hyperpolarized [1-(1)(3)C]pyruvate. Sci Transl Med. 2013; 5: 198ra108.

11

Swindle P, Ramadan S, Stanwell P, McCredie S, Russell P, Mountford C. Proton magnetic resonance spectroscopy of the central, transition and peripheral zones of the prostate: assignments and correlation with histopathology. MAGMA. 2008; 21: 423-34.

12

Drake RR, White KY, Fuller TW, Igwe E, Clements MA, Nyalwidhe JO, et al. Clinical collection and protein properties of expressed prostatic secretions as a source for biomarkers of prostatic disease. J Proteomics. 2009; 72: 907-17.

13

Ploussard G, de la Taille A. Urine biomarkers in prostate cancer. Nat Rev Urol. 2010; 7: 101-9.

14

Drake RR, Elschenbroich S, Lopez-Perez O, Kim Y, Ignatchenko V, Ignatchenko A, et al. In-depth proteomic analyses of direct expressed prostatic secretions. J Proteome Res. 2010; 9: 2109-16.

15

Kim Y, Ignatchenko V, Yao CQ, Kalatskaya I, Nyalwidhe JO, Lance RS, et al. Identification of differentially expressed proteins in direct expressed prostatic secretions of men with organ-confined versus extracapsular prostate cancer. Mol Cell Proteomics. 2012; 11: 1870-84.

16

Principe S, Jones EE, Kim Y, Sinha A, Nyalwidhe JO, Brooks J, et al. In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. Proteomics. 2013; 13: 1667-71.

17

Principe S, Kim Y, Fontana S, Ignatchenko V, Nyalwidhe JO, Lance RS, et al. Identification of prostate-enriched proteins by in-depth proteomic analyses of expressed prostatic secretions in urine. J Proteome Res. 2012; 11: 2386-96.

18

Want EJ, Masson P, Michopoulos F, Wilson ID, Theodoridis G, Plumb RS, et al. Global metabolic profiling of animal and human tissues via UPLC-MS. Nat Protoc. 2013; 8: 17-32.

19

Paglia G, Hrafnsdottir S, Magnusdottir M, Fleming RM, Thorlacius S, Palsson BO, et al. Monitoring metabolites consumption and secretion in cultured cells using ultra-performance liquid chromatography quadrupole-time of flight mass spectrometry (UPLC-Q-ToF-MS). Anal Bioanal Chem. 2012; 402: 1183-98.

20

Rosen Vollmar AK, Rattray NJW, Cai Y, Santos-Neto AJ, Deziel NC, Jukic AMZ, et al. Normalizing untargeted periconceptional urinary metabolomics data: a comparison of approaches. Metabolites. 2019; 9: 198.

21

Filzmoser P, Walczak B. What can go wrong at the data normalization step for identification of biomarkers? J Chromatogr A. 2014; 1362: 194-205.

22

Saeed AI, Sharov V, White J, Li J, Liang W, Bhagabati N, et al. TM4: a free, open-source system for microarray data management and analysis. Biotechniques. 2003; 34: 374-8.

23

Chong J, Soufan O, Li C, Caraus I, Li S, Bourque G, et al. Metaboanalyst 4.0: towards more transparent and integrative metabolomics analysis. Nucleic Acids Res. 2018; 46: W486-94.

24

Blodgett TM, Meltzer CC, Townsend DW. PET/CT: form and function. Radiology. 2007; 242: 360-85.

25

Zhang A, Yan G, Han Y, Wang X. Metabolomics approaches and applications in prostate cancer research. Appl Biochem Biotechnol. 2014; 174: 6-12.

26

Jiang Y, Cheng X, Wang C, Ma Y. Quantitative determination of sarcosine and related compounds in urinary samples by liquid chromatography with tandem mass spectrometry. Anal Chem. 2010; 82: 9022-7.

27

Jentzmik F, Stephan C, Lein M, Miller K, Kamlage B, Bethan B, et al. Sarcosine in prostate cancer tissue is not a differential metabolite for prostate cancer aggressiveness and biochemical progression. J Urol. 2011; 185: 706-11.

28

Jentzmik F, Stephan C, Miller K, Schrader M, Erbersdobler A, Kristiansen G, et al. Sarcosine in urine after digital rectal examination fails as a marker in prostate cancer detection and identification of aggressive tumours. Eur Urol. 2010; 58: 12-8; discussion 20-1.

29

Cao DL, Ye DW, Zhu Y, Zhang HL, Wang YX, Yao XD. Efforts to resolve the contradictions in early diagnosis of prostate cancer: a comparison of different algorithms of sarcosine in urine. Prostate Cancer Prostatic Dis. 2011; 14: 166-72.

30

McDunn JE, Li Z, Adam KP, Neri BP, Wolfert RL, Milburn MV, et al. Metabolomic signatures of aggressive prostate cancer. Prostate. 2013; 73: 1547-60.

31

Giunchi F, Fiorentino M, Loda M. The metabolic landscape of prostate cancer. Eur Urol Oncol. 2019; 2: 28-36.

32

Keshet R, Erez A. Arginine and the metabolic regulation of nitric oxide synthesis in cancer. Dis Model Mech. 2018; 11: dmm033332.

33

Husson A, Brasse-Lagnel C, Fairand A, Renouf S, Lavoinne A. Argininosuccinate synthetase from the urea cycle to the citrulline-no cycle. Eur J Biochem. 2003; 270: 1887-99.

34

Rhee HJ, Kim EJ, Lee JK. Physiological polyamines: simple primordial stress molecules. J Cell Mol Med. 2007; 11: 685-703.

35

Liang X, Zhang L, Natarajan SK, Becker DF. Proline mechanisms of stress survival. Antioxid Redox Signal. 2013; 19: 998-1011.

36

Sestili P, Ambrogini P, Barbieri E, Sartini S, Fimognari C, Calcabrini C, et al. New insights into the trophic and cytoprotective effects of creatine in in vitro and in vivo models of cell maturation. Amino Acids. 2016; 48: 1897-911.

37

Delage B, Fennell DA, Nicholson L, McNeish I, Lemoine NR, Crook T, et al. Arginine deprivation and argininosuccinate synthetase expression in the treatment of cancer. Int J Cancer. 2010; 126: 2762-72.

38

Mu D, Gao Z, Guo H, Zhou G, Sun B. Sodium butyrate induces growth inhibition and apoptosis in human prostate cancer DU145 cells by up-regulation of the expression of annexin A1. PLoS One. 2013; 8: e74922.

39

Venkateswaran N, Conacci-Sorrell M. Kynurenine: an oncometabolite in colon cancer. Cell Stress. 2020; 4: 24-6.

40

Heng B, Lim CK, Lovejoy DB, Bessede A, Gluch L, Guillemin GJ. Understanding the role of the kynurenine pathway in human breast cancer immunobiology. Oncotarget. 2016; 7: 6506-20.

Cancer Biology & Medicine
Pages 604-615
Cite this article:
Drago D, Andolfo A, Mosca E, et al. A novel expressed prostatic secretion (EPS)-urine metabolomic signature for the diagnosis of clinically significant prostate cancer. Cancer Biology & Medicine, 2021, 18(2): 604-615. https://doi.org/10.20892/j.issn.2095-3941.2020.0617

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Received: 02 October 2020
Accepted: 25 December 2020
Published: 01 May 2021
©2021 Cancer Biology & Medicine.

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