Metabolomic Study of Human Tissue and Urine in Clear Cell Renal Carcinoma by LC-HRMS and PLS-DA

Overview

Journal Anal Bioanal Chem

Specialty Chemistry

Date 2018 Apr 17

PMID 29658093

Citations 21

Authors

Joanna Niziol

Vincent Bonifay

Krzysztof Ossolinski

Tadeusz Ossolinski

Anna Ossolinska

Jan Sunner

Iwona Beech

Adrian Arendowski

Tomasz Ruman

Affiliations

Soon will be listed here.

Abstract

Renal cell carcinoma (RCC) is the most prevalent and lethal malignancy of the kidney. Despite all the efforts made, no tissue biomarker is currently used in the clinical management of patients with kidney cancer. A search for possible biomarkers in urine for clear cell renal cell carcinoma (ccRCC) has been conducted. Non-targeted metabolomic analyses were performed on paired samples of surgically removed renal cancer and normal tissue, as well as on urine samples. Extracts were analyzed by liquid chromatography/high-resolution mass spectrometry (LC-HRMS). Hydroxybutyrylcarnitine, decanoylcarnitine, propanoylcarnitine, carnitine, dodecanoylcarnitine, and norepinephrine sulfate were found in much higher concentrations in both cancer tissues (compared with the paired normal tissue) and in urine of cancer patients (compared with control urine). In contrast, riboflavin and acetylaspartylglutamate (NAAG) were present at significantly higher concentrations both in normal kidney tissue as well as in urine samples of healthy persons. This preliminary study resulted in the identification of several compounds that may be considered potential clear cell renal carcinoma biomarkers. Graphical abstract PLS-DA plot based on LC-MS data for normal and cancer human tissue samples. The aim of this work was the identification of up- and downregulated compounds that could potentially serve as renal cancer biomarkers.

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References

Scheltema R, Jankevics A, Jansen R, Swertz M, Breitling R . PeakML/mzMatch: a file format, Java library, R library, and tool-chain for mass spectrometry data analysis. Anal Chem. 2011; 83(7):2786-93. DOI: 10.1021/ac2000994. View

Gil A, Guedes de Pinho P, Monteiro M, Duarte I . NMR metabolomics of renal cancer: an overview. Bioanalysis. 2015; 7(18):2361-2374. DOI: 10.4155/bio.15.167. View

Hakimi A, Reznik E, Lee C, Creighton C, Brannon A, Luna A . An Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma. Cancer Cell. 2016; 29(1):104-116. PMC: 4809063. DOI: 10.1016/j.ccell.2015.12.004. View

Catchpole G, Platzer A, Weikert C, Kempkensteffen C, Johannsen M, Krause H . Metabolic profiling reveals key metabolic features of renal cell carcinoma. J Cell Mol Med. 2009; 15(1):109-18. PMC: 3822498. DOI: 10.1111/j.1582-4934.2009.00939.x. View

Xia J, Wishart D . Using MetaboAnalyst 3.0 for Comprehensive Metabolomics Data Analysis. Curr Protoc Bioinformatics. 2016; 55:14.10.1-14.10.91. DOI: 10.1002/cpbi.11. View

Gowda G, Zhang S, Gu H, Asiago V, Shanaiah N, Raftery D . Metabolomics-based methods for early disease diagnostics. Expert Rev Mol Diagn. 2008; 8(5):617-33. PMC: 3890417. DOI: 10.1586/14737159.8.5.617. View

Beloribi-Djefaflia S, Vasseur S, Guillaumond F . Lipid metabolic reprogramming in cancer cells. Oncogenesis. 2016; 5:e189. PMC: 4728678. DOI: 10.1038/oncsis.2015.49. View

Godley P, Taylor M . Renal cell carcinoma. Curr Opin Oncol. 2001; 13(3):199-203. DOI: 10.1097/00001622-200105000-00012. View

Fisel P, Kruck S, Winter S, Bedke J, Hennenlotter J, Nies A . DNA methylation of the SLC16A3 promoter regulates expression of the human lactate transporter MCT4 in renal cancer with consequences for clinical outcome. Clin Cancer Res. 2013; 19(18):5170-81. DOI: 10.1158/1078-0432.CCR-13-1180. View

10.

Coyle J . The nagging question of the function of N-acetylaspartylglutamate. Neurobiol Dis. 1997; 4(3-4):231-8. DOI: 10.1006/nbdi.1997.0153. View

11.

Cairns R, Harris I, Mak T . Regulation of cancer cell metabolism. Nat Rev Cancer. 2011; 11(2):85-95. DOI: 10.1038/nrc2981. View

12.

Schmidt-Sommerfeld E, Penn D, Duran M, Bennett M, Santer R, Stanley C . Detection of inborn errors of fatty acid oxidation from acylcarnitine analysis of plasma and blood spots with the radioisotopic exchange-high-performance liquid chromatographic method. J Pediatr. 1993; 122(5 Pt 1):708-14. DOI: 10.1016/s0022-3476(06)80009-0. View

13.

Wishart D, Jewison T, Guo A, Wilson M, Knox C, Liu Y . HMDB 3.0--The Human Metabolome Database in 2013. Nucleic Acids Res. 2012; 41(Database issue):D801-7. PMC: 3531200. DOI: 10.1093/nar/gks1065. View

14.

Gao H, Dong B, Jia J, Zhu H, Diao C, Yan Z . 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):753-61. DOI: 10.1007/s00432-011-1134-6. View

15.

Zira A, Theocharis S, Mitropoulos D, Migdalis V, Mikros E . (1)H NMR metabonomic analysis in renal cell carcinoma: a possible diagnostic tool. J Proteome Res. 2010; 9(8):4038-44. DOI: 10.1021/pr100226m. View

16.

de Vogel S, Dindore V, van Engeland M, Goldbohm R, van den Brandt P, Weijenberg M . Dietary folate, methionine, riboflavin, and vitamin B-6 and risk of sporadic colorectal cancer. J Nutr. 2008; 138(12):2372-8. DOI: 10.3945/jn.108.091157. View

17.

Sastry K, Karpova Y, Prokopovich S, Smith A, Essau B, Gersappe A . Epinephrine protects cancer cells from apoptosis via activation of cAMP-dependent protein kinase and BAD phosphorylation. J Biol Chem. 2007; 282(19):14094-100. DOI: 10.1074/jbc.M611370200. View

18.

Bleumer I, Oosterwijk E, De Mulder P, Mulders P . Immunotherapy for renal cell carcinoma. Eur Urol. 2003; 44(1):65-75. DOI: 10.1016/s0302-2838(03)00191-x. View

19.

Powers H . Riboflavin (vitamin B-2) and health. Am J Clin Nutr. 2003; 77(6):1352-60. DOI: 10.1093/ajcn/77.6.1352. View

20.

Linehan W, Srinivasan R, Schmidt L . The genetic basis of kidney cancer: a metabolic disease. Nat Rev Urol. 2010; 7(5):277-85. PMC: 2929006. DOI: 10.1038/nrurol.2010.47. View