Untargeted LC-QTOF (ESI +) MS Analysis of Small Serum Metabolites Related to Prostate Cancer and Prostate Specific Antigen

Ramona Maria Maxim, Carmen Socaciu, Anca Dana Buzoianu, Raluca Maria Pop, Florina Romanciuc

Abstract


Prostate cancer has an increasing incidence and there is an urgent need for development of new serum biomarkers for early diagnostic as the ones known are ineffective. The aim of the study was to use untargeted metabolomics in order to identify and characterize small metabolite fingerprints in patients with normal vs pathologic values of PSA ( previously determined by electrochemiluminiscence).

A cohort of one hundred patients with different Prostate Specific amtigen values were investigated by untargeted metabolomics. The serum small metabolite profile determined by high performance liquid chromatography coupled with mass spectrometry, LC-QTOF(ESI+)MS in order to identify specific biomarkers, for normal patient group (PSA = 0-4 ng.ml) and four pathologic groups, having PSA values from 4 to >1000 ng/ml.

The major molecules identified in the samples were polar phospholipids, maily lysophosphatidyl choline derivatives, having m/z values from 496 to 524, like LPC(O-16:0/O-1:0), LPC(18:1/2:0) or PS(18:1(9Z)/0:0), LPC(18:2(9Z,12Z)/0:0 and their isomers and  LPC(O-18:1(11Z)/2:0), respectively. Also, small molecules (free fatty acids and prostaglandin derivatives) were identified and are significantly different in pathologic vs normal serum samples. Generally the pathologic samples had increased concentrations of all above mentioned molecules. The Principal Component analysis showed , by plot and loadings scores, significant clustering of normal vs pathological groups.


Keywords


prostate specific antigen, small metabolites, untargeted metabolomics, high performance liquid chromatography, mass spectrometry

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References


Antenor JA, Roehl KA, Eggener SE et al. (2005) Preoperative PSA and progression- free survival after radical prostatectomy for Stage T1c disease. Urology; 66:156 –160.

Aebersold R. and M. Mann (2003). Mass spectrometry-based proteomics, Nature, vol. 422, no. 6928, pp. 198–207.

Barry MJ (2001). Clinical practice. Prostate-specific-antigen testing for early diagnosis of prostate cancer. New England Journal of Medicine. 344(18):1373-1377.

Da Costa, Danielly Cristiny Ferraz; Casanova, Fabiana Alves; Quarti, Julia; Malheiros, Maitê Santos; Sanches, Daniel; dos Santos, Patricia Souza; Fialho, Eliane; Silva, Jerson L. (2012) Identification of Plasma Lipid Biomarkers for Prostate Cancer by Lipidomics and Bioinformatics; PLoS ONE, Vol. 7 Issue 11.

Diamandis EP, Yu H (1997). Nonprostatic sources of prostate-specific antigen. Urol Clin North Am. 24: 275-82.

Dhanasekaran,S.M. et al. (2001). Delineation of prognostic biomarkers in prostate cancer. Nature, 412, 822–826.

Hankey, B.F., Feuer, E.J., Clegg, L.X., Hayes, R.B., Legler, J.M., Prorok, P.C., Ries, L.A., Merrill, R.M.,and Kaplan, R.S., (1999), J. Nat. Cancer Inst., vol. 91, pp. 1017–1024.

Haythorn, M.R.; Ablin R.J., (2011). Prostate-specific antigen testing across the spectrum of prostate cancer. Biomark. Med. 5, 515–526.

Henttu P, Vihko P. (1994). Prostate-specific Anigen and Human Glandular Kallikrein: Two Kallikreins of the Human Prostate. Ann Med. 26:157-164.

F. Jentzmik et al. (2010). Sarcosine in Urine after Digital Rectal Examination Fails as a Marker in Prostate Cancer Detection and Identification of Aggressive Tumours". European Urology 58(1): 12–18.

Loeb Stacy, William J. Catalona. (2008). What to Do with an Abnormal PSA Test, The Oncologist; 13:299–305.

P. G. Lokhov, M. I. Dashtiev, L. V. Bondartsov, A. V. Lisitsa, S. A. Moshkovskii, and A. I. (2008). Archakov Metabolic Fingerprinting of Blood plasma from Patients with Prostate Cancer, Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry, Vol. 4, 37-41.

Mistry, K.; Cable, G. (2003) Meta-analysis of prostate-specific antigen and digital rectal examination as screening tests for prostate carcinoma. J. Am. Board Fam. Pract., 16, 95–101.

Oh WK, Hurwitz M, D'Amico AV, et al. (2003). Neoplasms of the Prostate. Cancer Medicine. Hamilton, Canada: BC Decker Inc.

Prestigiacomo AF, Stamey TA. (1995). Clinical usefulness of free and complexed PSA. Clin Lab Invest. 55 Suppl 221:32-34.

J. R. Prensner, M. A. Rubin, J. T. Wei, A. M. Chinnaiyan, (2012). Beyond PSA: The Next Generation of Prostate Cancer Biomarkers. Sci. Transl. Med. 4.

Polascik TJ, Oesterling JE, Partin AW. (1999). Prostate specific antigen. A decade of discovery—what we have learned and where we are going. J Urol. 162: 293-306.

Pavlou M. and E. P. Diamandis (2009). The Search for New Prostate Cancer Biomarkers Continues. Clinical Chemistry 55 (7): 1277–1279.

Rao AR, Motiwala HG, Karim OM. (2008). The discovery of prostate-specific antigen. BJU Int; 101: 5-10.

Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM. (2009). Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. 457(7231):910-4.

Struys et al. (2010). Serum sarcosine is not a marker for prostate cancer". Annals Clinical Biochemistry 47 (Pt 3): 282.

Schroder, F.H.; van der Cruijsen-Koeter, I.; de Koning, H.J.; Vis, A.N.; Hoedemaeker, R.F.; Kranse, (2000). R. Prostate cancer detection at low prostate specific antigen. J. Urol., 163, 806–812.

Tessitore Alessandra, Agata Gaggiano, Germana Cicciarelli, Daniela Verzella, Daria Capece, Mariafausta Fischietti, Francesca Zazzeroni, and Edoardo Alesse (2013). Serum Biomarkers Identification by Mass Spectrometry in High-Mortality Tumors; International Journal of Proteomics, Article ID 125858, 15 pages.

Tomlins,S.A. et al. (2006) Integrative molecular concept modeling of prostate cancer progression. Nat. Genet., 39, 41–51.

Vuckovic D., (2012). Current trends and challenges in sample preparation for global metabolomics using liquid chromatography–mass spectrometry, Anal Bioanal Chem 403:1523–1548.

Yates J. R. III, (2004) Mass spectral analysis in proteomics, Annual Review of Biophysics and Biomolecular Structure, vol. 33, pp. 297–316.

Zhao Z, Xiao Y, Elson P, Tan H, Plummer SJ, Berk M, Aung PP, Lavery IC, Achkar JP, Li L, Casey G, Xu Y., (2007)., Plasma lysophosphatidylcholine levels: potential biomarkers for colorectal cancer. J Clin Oncol., 25(19):2696-701

Zhang WM, Leinonen J, Kalkkinen N, Dowell B, Stenman UH. (1995). Purification and Characterization of Different Molecular Forms of Prostate-Specific Antigen in Human Seminal Fluid. Clin Chem. 41/11:1567-1573.

Da Costa X, Mao J, Ai J, Deng Y, Roth MR, et al. (2012) Identification of Plasma Lipid Biomarkers for Prostate Cancer by Lipidomics and Bioinformatics. Plos One 7 (11).

http://www.cancer.gov/cancertopics/types/prostateProstate Cancer Foundation. Home page of Prostate Cancer Foundation. http://www.prostatecancerfoundation.org.

http://www.lipidmaps.org/tools/ms/LMSD_search_mass_options.php




DOI: http://dx.doi.org/10.15835/buasvmcn-fst:10847

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