Mass spectrometry-based metabolomic profiling of prostate cancer - a pilot study

Krzysztof Ossoliński , Joanna Nizioł , Adrian Arendowski , Anna Ossolińska , Tadeusz Ossoliński , Jakub Kucharz , Paweł Wiechno , Tomasz Ruman

Journal of Cancer Metastasis and Treatment ›› 2019, Vol. 5 : 1

PDF
Journal of Cancer Metastasis and Treatment ›› 2019, Vol. 5:1 DOI: 10.20517/2394-4722.2018.63
Original Article
review-article

Mass spectrometry-based metabolomic profiling of prostate cancer - a pilot study

Author information +
History +
PDF

Abstract

Aim: Prostate cancer (PCa) is the most commonly diagnosed non-skin cancer among men. Serum prostate-specific antigen level is used as a standard PCa biomarker for over 20 years. However, it has only 33% specificity and 86% sensitivity (for the cutoff value for prostate biopsy of > 4 ng/mL). This leads to overdiagnosis and overtreatment. In-depth insight into PCa metabolomics enables discovery of novel PCa biomarkers.

Methods: Metabolomic alternation in PCa serum, urine and interstitial fluid was examined using gold-nanoparticle-based laser mass spectrometry imaging. This study included 5 patients who underwent prostate biopsy with positive result, 5 patients with negative result and 10 healthy controls.

Results: Over two hundred differentiating metabolites (87 in urine, 54 in serum and 78 in interstitial fluid) were detected. Four, twenty two and ten metabolites from urine, serum and interstitial fluid respectively showed statistical significant differential abundance between cancer and control group.

Conclusion: Comprehensive metabolomic profile of PCa has been identified. Out of 36 metabolites, 20 were identified and should be further evaluated in clinical trials as a potential PCa biomarker. Urine concentration of triglyceride (12:0/20:1) showed over 10 times higher abundance in PCa samples in comparison to healthy controls and is considered the most promising potential biomarker.

Keywords

Prostate cancer / biomarker / metabolomics / mass spectrometry

Cite this article

Download citation ▾
Krzysztof Ossoliński, Joanna Nizioł, Adrian Arendowski, Anna Ossolińska, Tadeusz Ossoliński, Jakub Kucharz, Paweł Wiechno, Tomasz Ruman. Mass spectrometry-based metabolomic profiling of prostate cancer - a pilot study. Journal of Cancer Metastasis and Treatment, 2019, 5: 1 DOI:10.20517/2394-4722.2018.63

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Brawley OW.Prostate cancer epidemiology in the United States..World J Urol2012;30:195-200

[2]

Schröder FH,Roobol MJ,Ciatto S.Screening and prostate-cancer mortality in a randomized European study..N Engl J Med2009;360:1320-8

[3]

Hugosson J,Aus G,Khatami A.Mortality results from the Göteborg randomised population-based prostate-cancer screening trial..Lancet Oncol2010;11:725-32 PMCID:PMC4089887

[4]

Andriole GL,Grubb RL,Chia D.Mortality results from a randomized prostate-cancer screening trial..N Engl J Med2009;360:1310-9 PMCID:PMC2944770

[5]

Hayes JH.Screening for prostate cancer with the prostate-specific antigen test: a review of current evidence..JAMA2014;311:1143-9

[6]

Van Neste L,Dijkstra S,Cornel EB.Detection of high-grade prostate cancer using a urinary molecular biomarker-based risk score..Eur Urol2016;70:740-8

[7]

Govers TM,Vlaeminck-Guillem V,Stief CG.Cost-effectiveness of SelectMDx for prostate cancer in four European countries: a comparative modeling study..Prostate Cancer Prostatic Dis2018;

[8]

Patti GJ,Siuzdak G.Innovation: metabolomics: the apogee of the omics trilogy..Nat Rev Mol Cell Biol2012;13:263-9 PMCID:PMC3682684

[9]

Diamandis EP.Mass spectrometry as a diagnostic and a cancer biomarker discovery tool: opportunities and potential limitations..Mol Cell Proteomics2004;3:367-78

[10]

Yang J,Guo H,Gao R.Identifying serum biomarkers for ovarian cancer by screening with surface-enhanced laser desorption/ionization mass spectrometry and the artificial neural network..Int J Gynecol Cancer2013;23:667-72

[11]

Wright GL Jr,Leung SM,Adam BL.Proteinchip(R) surface enhanced laser desorption/ionization (SELDI) mass spectrometry: a novel protein biochip technology for detection of prostate cancer biomarkers in complex protein mixtures..Prostate Cancer Prostatic Dis1999;2:264-76

[12]

Ocak S,Massion PP.Mass spectrometry-based proteomic profiling of lung cancer..Proc Am Thorac Soc2009;6:159-70 PMCID:PMC2674226

[13]

Martínez-Aguilar J,Nicholson J,McKay MJ.Quantitative mass spectrometry for colorectal cancer proteomics..Proteomics Clin Appl2013;7:42-54

[14]

Wu B,Fishman D,Mor G.Ovarian cancer classification based on mass spectrometry analysis of sera..Cancer Inform2007;2:123-32 PMCID:PMC2675484

[15]

Nizioł J,Ossoliński T,Bonifay V.Surface-transfer mass spectrometry imaging of renal tissue on gold nanoparticle enhanced target..Anal Chem2016;88:7365-71

[16]

Whelan SA,Lu M,Saxton RE.Mass spectrometry (LC-MS/MS) identified proteomic biosignatures of breast cancer in proximal fluid..J Proteome Res2012;11:5034-45 PMCID:PMC3521600

[17]

Xue R,Zhang S,Liu T.Investigation of volatile biomarkers in liver cancer blood using solid-phase microextraction and gas chromatography/mass spectrometry..Rapid Commun Mass Spectrom2008;22:1181-6

[18]

Lucarelli G,Galleggiante V,Palazzo S.Metabolomic profiling for the identification of novel diagnostic markers in prostate cancer..Expert Rev Mol Diagn2015;15:1211-24

[19]

Ferro M,Bruzzese D,Mazzarella C.Improving the prediction of pathologic outcomes in patients undergoing radical prostatectomy: the value of prostate cancer antigen 3 (PCA3), prostate health index (phi) and sarcosine..Anticancer Res2015;35:1017-23

[20]

de Vogel S,Meyer K,Nygård O.Sarcosine and other metabolites along the choline oxidation pathway in relation to prostate cancer - a large nested case-control study within the JANUS cohort in Norway..Int J Cancer2014;134:197-206

[21]

de Cobelli O,Tagliabue E,Galasso G.Body mass index was associated with upstaging and upgrading in patients with low-risk prostate cancer who met the inclusion criteria for active surveillance..Urol Oncol2015;33:201

[22]

Ferro M,Bruzzese D,Perdonà S.Low serum total testosterone level as a predictor of upstaging and upgrading in low-risk prostate cancer patients meeting the inclusion criteria for active surveillance..Oncotarget2017;8:18424-34 PMCID:PMC5392340

[23]

Sekuła J,Rode W.Gold nanoparticle-enhanced target (AuNPET) as universal solution for laser desorption/ionization mass spectrometry analysis and imaging of low molecular weight compounds..Anal Chim Acta.2015;875:61-72

[24]

Cacciatore S,Bango C,Tyekucheva S.Metabolic profiling in formalin-fixed and paraffin-embedded prostate cancer tissues..Mol Cancer Res2017;15:439-47 PMCID:PMC5552883

[25]

Sund M.Tumor stroma derived biomarkers in cancer..Cancer Metastasis Rev2009;28:177-83 PMCID:PMC4476244

[26]

Albini A.The tumour microenvironment as a target for chemoprevention..Nat Rev Cancer2007;7:139-47

[27]

Liu Y,Ghesani NV.Dominant uptake of fatty acid over glucose by prostate cells: a potential new diagnostic and therapeutic approach..Anticancer Res2010;30:369-74

[28]

Beloribi-Djefaflia S,Guillaumond F.Lipid metabolic reprogramming in cancer cells..Oncogenesis2016;5:e189 PMCID:PMC4728678

[29]

Liu IJ,Lai YH,Terris MK.Fluorodeoxyglucose positron emission tomography studies in diagnosis and staging of clinically organ-confined prostate cancer..Urology2001;57:108-11

[30]

Mostaghel EA,Pelton K,Montgomery RB.Impact of circulating cholesterol levels on growth and intratumoral androgen concentration of prostate tumors..PLoS One2012;7:e30062 PMCID:PMC3261168

[31]

Twiddy AL,Wasan KM.Cholesterol as a potential target for castration-resistant prostate cancer..Pharm Res2011;28:423-37

[32]

Montgomery RB,Vessella R,Kalhorn TF.Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth..Cancer Res2008;68:4447-54 PMCID:PMC2536685

[33]

Stopsack KH,Sinnott JA,Tyekucheva S.Cholesterol metabolism and prostate cancer lethality..Cancer Res2016;76:4785-90 PMCID:PMC4987257

[34]

Allott EH,Cooperberg MR,Aronson WJ.Serum lipid profile and risk of prostate cancer recurrence: results from the SEARCH database..Cancer Epidemiol Biomarkers Prev2014;23:2349-56 PMCID:PMC4221498

[35]

Platz EA,Goodman PJ,Figg WD.Men with low serum cholesterol have a lower risk of high-grade prostate cancer in the placebo arm of the prostate cancer prevention trial..Cancer Epidemiol Biomarkers Prev2009;18:2807-13 PMCID:PMC2877916

[36]

Mondul AM,Helzlsouer KJ.Association between plasma total cholesterol concentration and incident prostate cancer in the CLUE II cohort..Cancer Causes Control2009;21:61-8 PMCID:PMC3004752

[37]

Kok DE,Aben KK,Swinkels DW.Blood lipid levels and prostate cancer risk; a cohort study..Prostate Cancer Prostatic Dis2011;14:340-5

[38]

Wuermli L,Henz S,Riesen WF.Hypertriglyceridemia as a possible risk factor for prostate cancer..Prostate Cancer Prostatic Dis2005;8:316-20

[39]

Platz EA,Giovannucci E.Association between plasma cholesterol and prostate cancer in the PSA era..Int J Cancer2008;123:1693-8 PMCID:PMC2536746

[40]

Eberlin LS,Costa AB,Cheng L.Cholesterol sulfate imaging in human prostate cancer tissue by desorption electrospray ionization mass spectrometry..Anal Chem2010;82:3430-4 PMCID:PMC2872194

[41]

Liu Y.Fatty acid oxidation is a dominant bioenergetic pathway in prostate cancer..Prostate Cancer Prostatic Dis2006;9:230-4

[42]

Flavin R,Nguyen PL.Fatty acid synthase as a potential therapeutic target in cancer..Future Oncol2010;6:551-62 PMCID:PMC3197858

[43]

Giskeødegård GF,Bertilsson H,Kristiansen KA.Metabolic markers in blood can separate prostate cancer from benign prostatic hyperplasia..Br J Cancer2015;113:1712-9 PMCID:PMC4702000

[44]

Saylor PJ,Smith MR.Prospective study of changes in the metabolomic profiles of men during their first three months of androgen deprivation therapy for prostate cancer..Clin Cancer Res2012;18:3677-85 PMCID:PMC3661207

[45]

Fu YQ,Yang B.Effect of individual omega-3 fatty acids on the risk of prostate cancer: a systematic review and dose-response meta-analysis of prospective cohort studies..J Epidemiol2015;25:261-74 PMCID:PMC4375280

[46]

Murphy AB,Martin IK,Hollowell CM.Vitamin D deficiency predicts prostate biopsy outcomes..Clin Cancer Res2014;20:2289-99 PMCID:PMC4104275

[47]

Gilbert R,Fraser WD,Hamdy F.Associations of circulating 25-hydroxyvitamin D with prostate cancer diagnosis, stage and grade..Int J Cancer2011;131:1187-96 PMCID:PMC3378478

[48]

Ben-Eltriki M,Guns ES.Calcitriol in combination therapy for prostate cancer: pharmacokinetic and pharmacodynamic interactions..J Cancer2016;7:391-407 PMCID:PMC4749360

[49]

Marshall DT,Garrett-Mayer E,Hollis BW.Vitamin D3 supplementation at 4000 international units per day for one year results in a decrease of positive cores at repeat biopsy in subjects with low-risk prostate cancer under active surveillance..J Clin Endocrinol Metab2012;97:2315-24 PMCID:PMC3387395

[50]

Beer TM,Venner PM,Chatta GS.Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgen-independent prostate cancer: a report from the ASCENT investigators..J Clin Oncol2007;25:669-74

[51]

Krishnan AV,Nonn L,Peehl DM.Calcitriol as a chemopreventive and therapeutic agent in prostate cancer: role of anti-inflammatory activity..J Bone Miner Res2007;22:V74-80

[52]

Moreno J,Feldman D.Molecular mechanisms mediating the anti-proliferative effects of Vitamin D in prostate cancer..J Steroid Biochem Mol Biol2005;97:31-6

[53]

Podmore ID,Herbert KE,Mistry P.Vitamin C exhibits pro-oxidant properties..Nature1998;392:559

[54]

Davies O,Smallbone K.Characterisation of multiple substrate-specific (d)ITP/(d)XTPase and modelling of deaminated purine nucleotide metabolism..BMB Rep2012;45:259-64

[55]

Ji D,Cui J,Pavlov YI.Measuring deaminated nucleotide surveillance enzyme ITPA activity with an ATP-releasing nucleotide chimera..Nucleic Acids Res2017;45:11515-24 PMCID:PMC5714213

AI Summary AI Mindmap
PDF

13

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/