Metabolomic Heterogeneity of Urogenital Tract Cancers Analyzed by Complementary Chromatographic Techniques Coupled with Mass Spectrometry

Author(s): Arlette Yumba-Mpanga, Wiktoria Struck-Lewicka, Renata Wawrzyniak, Marcin Markuszewski, Marek Roslan, Roman Kaliszan, Michał Jan Markuszewski*.

Journal Name: Current Medicinal Chemistry

Volume 26 , Issue 1 , 2019

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Abstract:

Background: In regard to urogenital tract cancer studies, an estimated 340,650 new cases and 58,360 deaths from genital system cancer and about 141,140 new cases and 29330 deaths from urinary system were projected to occur in the United States in 2012. The main drawbacks of currently available diagnostic tests constitute the low specificity, costliness and quite high invasiveness.

Objective: The main goal of this pilot study was to determine and compare urine metabolic fingerprints in urogenital tract cancer patients and healthy controls.

Method: A comparative analysis of the metabolic profile of urine from 30 patients with cancer of the genitourinary system (bladder (n=10), kidney (n=10) and prostate (n=10)) and 30 healthy volunteers as a control group was provided by LC-TOF/MS and GCQqQ/ MS. The data analysis was performed by the use of U-Mann Whitney test or Student’s t-test, principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA).

Results: As a result, 33, 43, and 22 compounds were identified as statistically significant in bladder, prostate and kidney cancer, respectively, compared to healthy groups.

Conclusion: Diverse compounds such as purine, sugars, amino acids, nucleosides, organic acids which play a role in purine metabolism, in tricarboxylic acid cycle, in amino acid metabolism or in gut microbiota metabolism were identified. Only two metabolites namely glucocaffeic acid and lactic acid were found to be in common in studied three types of cancer.

Keywords: LC-MS, GC-MS, metabolomics, bladder cancer, kidney cancer, prostate cancer.

[1]
Siegel, R.; Naishadham, D.; Jemal, A. Cancer statistics, 2012. CA Cancer J. Clin., 2012, 62(1), 10-29.
[2]
Jemal, A.; Bray, F.; Center, M.M.; Ferlay, J.; Ward, E.; Forman, D. Global cancer statistics. CA Cancer J. Clin., 2011, 61(2), 69-90.
[3]
[4]
Wu, H.; Liu, T.; Ma, C.; Xue, R.; Deng, C.; Zeng, H.; Shen, X. GC/MS-based metabolomic approach to validate the role of urinary sarcosine and target biomarkers for human prostate cancer by microwave-assisted derivatization. Anal. Bioanal. Chem., 2011, 401(2), 635-646.
[5]
Alberice, J.V.; Amaral, A.F.; Armitage, E.G.; Lorente, J.A.; Algaba, F.; Carrilho, E.; Márquez, M.; García, A.; Malats, N.; Barbas, C. Searching for urine biomarkers of bladder cancer recurrence using a liquid chromatography-mass spectrometry and capillary electrophoresis-mass spectrometry metabolomics approach. J. Chromatogr. A, 2013, 1318, 163-170.
[6]
Herman, M.P.; Svatek, R.S.; Lotan, Y.; Karakiewizc, P.I.; Shariat, S.F. Urine-based biomarkers for the early detection and surveillance of non-muscle invasive bladder cancer. Minerva Urol. Nefrol., 2008, 60(4), 217-235.
[7]
Viswanath, S.; Zelhof, B.; Ho, E.; Sethia, K.; Mills, R. Is routine urine cytology useful in the haematuria clinic? Ann. R. Coll. Surg. Engl., 2008, 90(2), 153-155.
[8]
Shariat, S.F.; Karam, J.A.; Lotan, Y.; Karakiewizc, P.I. Critical evaluation of urinary markers for bladder cancer detection and monitoring. Rev. Urol., 2008, 10(2), 120-135.
[9]
Guo, A. Wang, X.; Gao, L.; Shi, J.; Sun, C.; Wan. Z. In Can Urol Assoc J: Canada, 2014, 8, E347-E352.
[10]
Landman, J.; Chang, Y.; Kavaler, E.; Droller, M.J.; Liu, B.C. Sensitivity and specificity of NMP-22, telomerase, and BTA in the detection of human bladder cancer. Urology, 1998, 52(3), 398-402.
[11]
Jain, P.; Surdas, R.; Aga, P.; Jain, M.; Kapoor, R.; Srivastava, A.; Mandhani, A. Renal cell carcinoma: Impact of mode of detection on its pathological characteristics. Indian J. Urol., 2009, 25(4), 479-482.
[12]
Morrissey, J.J.; London, A.N.; Luo, J.; Kharasch, E.D. Urinary biomarkers for the early diagnosis of kidney cancer. Mayo Clin. Proc., 2010, 85(5), 413-421.
[13]
Lindon, J.; Nicholson, J.; Holmes, E.; Everett, J. Metabonomics: Metabolic processes studied by NMR spectroscopy of biofluids. Concepts Magn. Reson., 2000, 12(5), 289-320.
[14]
Danielsson, R.; Allard, E.; Sjoberg, P.; Bergquist, J. Exploring liquid chromatography-mass spectrometry fingerprints of urine samples from patients with prostate or urinary bladder cancer. Chemom. Intell. Lab. Syst., 2011, 108(1), 33-48.
[15]
Markuszewski, M.J.; Struck, W.; Waszczuk-Jankowska, M.; Kaliszan, R. Metabolomic approach for determination of urinary nucleosides as potential tumor markers using electromigration techniques. Electrophoresis, 2010, 31(14), 2300-2310.
[16]
Catchpole, G.; Platzer, A.; Weikert, C.; Kempkensteffen, C.; Johannsen, M.; Krause, H.; Jung, K.; Miller, K.; Willmitzer, L.; Selbig, J.; Weikert, S. Metabolic profiling reveals key metabolic features of renal cell carcinoma. J. Cell. Mol. Med., 2011, 15(1), 109-118.
[17]
Pasikanti, K.K.; Esuvaranathan, K.; Hong, Y.; Ho, P.C.; Mahendran, R.; Raman Nee Mani, L.; Chiong, E.; Chan, E.C. Urinary metabotyping of bladder cancer using two-dimensional gas chromatography time-of-flight mass spectrometry. J. Proteome Res., 2013, 12(9), 3865-3873.
[18]
Perroud, B.; Lee, J.; Valkova, N.; Dhirapong, A.; Lin, P.Y.; Fiehn, O.; Kültz, D.; Weiss, R.H. Pathway analysis of kidney cancer using proteomics and metabolic profiling. Mol. Cancer, 2006, 5, 64.
[19]
Struck-Lewicka, W.; Kordalewska, M.; Bujak, R.; Yumba Mpanga, A.; Markuszewski, M.; Jacyna, J.; Matuszewski, M.; Kaliszan, R.; Markuszewski, M.J. Urine metabolic fingerprinting using LC-MS and GC-MS reveals metabolite changes in prostate cancer: A pilot study. J. Pharm. Biomed. Anal., 2015, 111, 351-361.
[20]
Godzien, J.; Ciborowski, M.; Angulo, S.; Barbas, C. From numbers to a biological sense: How the strategy chosen for metabolomics data treatment may affect final results. A practical example based on urine fingerprints obtained by LC-MS. Electrophoresis, 2013, 34(19), 2812-2826.
[21]
Naz, S.; García, A.; Barbas, C. Multiplatform analytical methodology for metabolic fingerprinting of lung tissue. Anal. Chem., 2013, 85(22), 10941-10948.
[22]
Wittmann, B.M.; Stirdivant, S.M.; Mitchell, M.W.; Wulff, J.E.; McDunn, J.E.; Li, Z.; Dennis-Barrie, A.; Neri, B.P.; Milburn, M.V.; Lotan, Y.; Wolfert, R.L. Bladder cancer biomarker discovery using global metabolomic profiling of urine. PLoS One, 2014, 9(12), e115870.
[23]
Ragan, T.J.; Bailey, A.P.; Gould, A.P.; Driscoll, P.C. Volume determination with two standards allows absolute quantification and improved chemometric analysis of metabolites by NMR from submicroliter samples. Anal. Chem., 2013, 85(24), 12046-12054.
[24]
Feng, B.; Zheng, M.H.; Zheng, Y.F.; Lu, A.G.; Li, J.W.; Wang, M.L.; Ma, J.J.; Xu, G.W.; Liu, B.Y.; Zhu, Z.G. Normal and modified urinary nucleosides represent novel biomarkers for colorectal cancer diagnosis and surgery monitoring. J. Gastroenterol. Hepatol., 2005, 20(12), 1913-1919.
[25]
Kim, K.R.; La, S.; Kim, A.; Kim, J.H.; Liebich, H.M. Capillary electrophoretic profiling and pattern recognition analysis of urinary nucleosides from uterine myoma and cervical cancer patients. J. Chromatogr. B Biomed. Sci. Appl., 2001, 754(1), 97-106.
[26]
Peng, J.; Chen, Y.T.; Chen, C.L.; Li, L. Development of a universal metabolome-standard method for long-term LC-MS metabolome profiling and its application for bladder cancer urine-metabolite-biomarker discovery. Anal. Chem., 2014, 86(13), 6540-6547.
[27]
Gao, H.; Dong, B.; Jia, J.; Zhu, H.; Diao, C.; Yan, Z.; Huang, Y.; Li, X. Application of ex vivo (1)H NMR metabonomics to the characterization and possible detection of renal cell carcinoma metastases. J. Cancer Res. Clin. Oncol., 2012, 138(5), 753-761.
[28]
Putluri, N.; Shojaie, A.; Vasu, V.T.; Vareed, S.K.; Nalluri, S.; Putluri, V.; Thangjam, G.S.; Panzitt, K.; Tallman, C.T.; Butler, C.; Sana, T.R.; Fischer, S.M.; Sica, G.; Brat, D.J.; Shi, H.; Palapattu, G.S.; Lotan, Y.; Weizer, A.Z.; Terris, M.K.; Shariat, S.F.; Michailidis, G.; Sreekumar, A. Metabolomic profiling reveals potential markers and bioprocesses altered in bladder cancer progression. Cancer Res., 2011, 71(24), 7376-7386.
[29]
Monteiro, M.S.; Carvalho, M.; Bastos, M.; Pinho, P.G. Biomarkers in renal cell carcinoma: a metabolomics approach. Metabolomics, 2014, 10(6), 1210-1222.
[30]
Chan, E.C.; Koh, P.K.; Mal, M.; Cheah, P.Y.; Eu, K.W.; Backshall, A.; Cavill, R.; Nicholson, J.K.; Keun, H.C. Metabolic profiling of human colorectal cancer using high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy and gas chromatography mass spectrometry (GC/MS). J. Proteome Res., 2009, 8(1), 352-361.
[31]
Pasikanti, K.K.; Norasmara, J.; Cai, S.; Mahendran, R.; Esuvaranathan, K.; Ho, P.C.; Chan, E.C. Metabolic footprinting of tumorigenic and nontumorigenic uroepithelial cells using two-dimensional gas chromatography time-of-flight mass spectrometry. Anal. Bioanal. Chem., 2010, 398(3), 1285-1293.
[32]
Kim, K. Taylor, S.L.; Ganti, S.; Guo, L.; Osier, M.V.; Weiss. Urine metabolomic analysis identifies potential biomarkers and pathogenic pathways in kidney cancer. 2011. Vol. 15, 293-303.
[33]
Sreekumar, A.; Poisson, L.M.; Rajendiran, T.M.; Khan, A.P.; Cao, Q.; Yu, J.; Laxman, B.; Mehra, R.; Lonigro, R.J.; Li, Y.; Nyati, M.K.; Ahsan, A.; Kalyana-Sundaram, S.; Han, B.; Cao, X.; Byun, J.; Omenn, G.S.; Ghosh, D.; Pennathur, S.; Alexander, D.C.; Berger, A.; Shuster, J.R.; Wei, J.T.; Varambally, S.; Beecher, C.; Chinnaiyan, A.M. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature, 2009, 457(7231), 910-914.
[34]
Zhang, T.; Wu, X.; Ke, C.; Yin, M.; Li, Z.; Fan, L.; Zhang, W.; Zhang, H.; Zhao, F.; Zhou, X.; Lou, G.; Li, K. Identification of potential biomarkers for ovarian cancer by urinary metabolomic profiling. J. Proteome Res., 2013, 12(1), 505-512.
[35]
Mondul, A.M.; Moore, S.C.; Weinstein, S.J.; Karoly, E.D.; Sampson, J.N.; Albanes, D. Metabolomic analysis of prostate cancer risk in a prospective cohort: The alpha-tocolpherol, beta-carotene cancer prevention (ATBC) study. Int. J. Cancer, 2015, 137(9), 2124-2132.
[36]
Dettmer, K.; Vogl, F.C.; Ritter, A.P.; Zhu, W.; Nürnberger, N.; Kreutz, M.; Oefner, P.J.; Gronwald, W.; Gottfried, E. Distinct metabolic differences between various human cancer and primary cells. Electrophoresis, 2013, 34(19), 2836-2847.
[37]
Li, P.; Tao, J.; Wei, D.; Yang, X.; Lu, Z.; Deng, X.; Cheng, Y.; Gu, J.; Yang, X.; Wang, Z.; Lu, Q.; Wang, J.; Yin, C. Serum metabolomic analysis of human upper urinary tract urothelial carcinoma. Tumour Biol., 2015, 36(10), 7531-7537.
[38]
Kaplan, K.; Liu, X.; Fu, Y.; Lin, H.; Meadows, G.; Siems, W.; Hill, H. Metabolic differences among melanoma and two prostate cancer cell lines by electrospray ion mobility mass spectrometry. Int. J. Ion Mobil. Spectrom., 2011, 14(4), 151-158.


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Article Details

VOLUME: 26
ISSUE: 1
Year: 2019
Page: [216 - 231]
Pages: 16
DOI: 10.2174/0929867324666171006150326

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