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Capillary electrophoresis–mass spectrometry in urinary proteome analysis: current applications and future developments

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Abstract

The development of noninvasive methods for diagnosis and prognosis of many diseases still remains a challenging task in clinical medicine. In recent years, protein separation and detection techniques have been refined such that they allow proteome screening of biological fluids with good reproducibility, accuracy, and real-time performance. The advancements in this field resulted in the initiation and conduction of many clinical studies aimed towards defining sensitive and selective biomarkers for disease or a pathological condition. In this review, we focus on the description of the state of the art proteomic platforms established or adapted to use urine as sample source for biomarker discovery. In the second part of this review, we will give an overview of recent clinical studies that used capillary electrophoresis–mass spectrometry (CE-MS) in urinary proteomics/peptidomics. Owing to its fast and accurate one-step screening method CE-MS allows resolution of the urinary small molecular weight proteome in high-throughput mode. This makes CE-MS well suited for use in large proteomic studies. The fact that urinary proteomic studies are not restricted to renal and urological disorders, but also enable assessment of systemic diseases like cardiovascular or infectious diseases, clearly demonstrates the considerably high potential that urine offers for biomarker discovery and for diagnosis, staging, prognosis, and progression monitoring of diseases.

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Abbreviations

2DE:

two-dimensional electrophoresis

BPH:

benign prostatic hyperplasia

CAD:

coronary artery disease

CE:

capillary electrophoresis

CE-MS:

CE-coupled mass spectrometry

CKD:

chronic kidney disease

DIGE:

differential in-gel electrophoresis

DN:

diabetic nephropathy

EOF:

electroosmotic flow

ESI-TOF-MS:

electrospray time-of-flight mass spectrometer

ESRD:

end-stage renal disease

FSGS:

focal segmental glomerulosclerosis

GVHD:

graft versus host disease

HSCT:

hematopoietic stem cell transplantation

IgA-N:

IgA nephropathy

LC:

liquid chromatography

MCD:

minimal change disease

MGN:

membranous glomerulonephritis

MS:

mass spectrometry

MudPIT:

multidimensional protein identification technology

Pca:

prostate cancer

SDS:

sodium dodecylsulfate

SELDI:

surface-enhanced laser desorption/ionization

UPJ:

ureteropelvic junction obstruction

References

  1. Goodsaid F, Bandow JE, Mischak H (2007) Proteomics Clin Appl 1:1526–1531

    Article  CAS  Google Scholar 

  2. Mischak H, Apweiler R, Banks RE, Conaway M, Coon JJ, Dominizak A, Ehrich JH, Fliser D, Girolami M, Hermjakob H, Hochstrasser DF, Jankowski V, Julian BA, Kolch W, Massy Z, Neususs C, Novak J, Peter K, Rossing K, Schanstra JP, Semmes OJ, Theodorescu D, Thongboonkerd V, Weissinger EM, Van Eyk JE, Yamamoto T (2007) Proteomics Clin Appl 1:148–156

    Article  CAS  Google Scholar 

  3. deVera IE, Katz JE, Agus DB (2006) Clin Adv Hematol Oncol 4:541–549

    Google Scholar 

  4. Good DM, Thongboonkerd V, Novak J, Bascands JL, Schanstra JP, Coon JJ, Dominiczak A, Mischak H (2007) J Proteome Res 6:4549–4555

    Article  CAS  Google Scholar 

  5. Lescuyer P, Hochstrasser D, Rabilloud T (2007) J Proteome Res 6:3371–3376

    Article  CAS  Google Scholar 

  6. Rai AJ (2007) Expert Rev Mol Diagn 7:545–553

    Article  CAS  Google Scholar 

  7. Wuhrer M (2007) Expert Rev Proteomics 4:135–136

    Article  CAS  Google Scholar 

  8. Tomana M, Novak J, Julian BA, Matousovic K, Konecny K, Mestecky J (1999) J Clin Invest 104:73–81

    Article  CAS  Google Scholar 

  9. Renfrow MB, Cooper HJ, Tomana M, Kulhavy R, Hiki Y, Toma K, Emmett MR, Mestecky J, Marshall AG, Novak J (2005) J Biol Chem 280:19136–19145

    Article  CAS  Google Scholar 

  10. Moldoveanu Z, Wyatt RJ, Lee JY, Tomana M, Julian BA, Mestecky J, Huang WQ, Anreddy SR, Hall S, Hastings MC, Lau KK, Cook WJ, Novak J (2007) Kidney Int 71:1148–1154

    Article  CAS  Google Scholar 

  11. Schaub S, Wilkins J, Weiler T, Sangster K, Rush D, Nickerson P (2004) Kidney Int 65:323–332

    Article  CAS  Google Scholar 

  12. Theodorescu D, Wittke S, Ross MM, Walden M, Conaway M, Just I, Mischak H, Frierson HF (2006) Lancet Oncol 7:230–240

    Article  CAS  Google Scholar 

  13. Vestergaard P, Leverett R (1958) J Lab Clin Med 51:211–218

    CAS  Google Scholar 

  14. Schiffer E, Mischak H, Novak J (2006) Proteomics 6:5615–5627

    Article  CAS  Google Scholar 

  15. Coon JJ, Zurbig P, Dakna M, Dominiczak AF, Decramer S, Fliser D, Frommberger M, Golovko I, Good DM, Herget-Rosenthal S, Jankowski J, Julian BA, Kellmann M, Kolch W, Massy Z, Novak J, Rossing K, Schanstra JP, Schiffer E, Theodorescu D, Vanholder R, Weissinger EM, Mischak H, Schmitt-Kopplin P (2008) Proteomics Clin Appl (in press)

  16. Yamamoto T, Langham RG, Ronco P, Knepper MA, Thongboonkerd V (2008) Proteomics 8:2156–2159

    Article  CAS  Google Scholar 

  17. Thongboonkerd V (2007) J Proteome Res 6:3881–3890

    Article  CAS  Google Scholar 

  18. Theodorescu D, Schiffer E, Bauer HW, Douwes F, Eichhorn F, Polley R, Schmidt T, Schofer W, Zuerbig P, Good DM, Coon JJ, Mischak H (2008) Proteomics Clin Appl 2:556–570

    Article  CAS  Google Scholar 

  19. Theodorescu D, Fliser D, Wittke S, Mischak H, Krebs R, Walden M, Ross M, Eltze E, Bettendorf O, Wulfing C, Semjonow A (2005) Electrophoresis 26:2797–2808

    Article  CAS  Google Scholar 

  20. Mischak H, Julian BA, Novak J (2007) Proteomics Clin Appl 1:792–804

    Article  CAS  Google Scholar 

  21. Thongboonkerd V (2007) Proteomics Clin Appl 1:780–791

    Article  CAS  Google Scholar 

  22. Bons JA, de BD, van Dieijen-Visser MP, Wodzig WK (2006) Clin Chim Acta 366:249–256

    Article  CAS  Google Scholar 

  23. Righetti PG, Campostrini N, Pascali J, Hamdan M, Astner H (2004) Eur J Mass Spectrom (Chichester, Eng) 10:335–348

    Article  CAS  Google Scholar 

  24. Ong SE, Mann M (2005) Nat Chem Biol 1:252–262

    Article  CAS  Google Scholar 

  25. Zybailov B, Coleman MK, Florens L, Washburn MP (2005) Anal Chem 77:6218–6224

    Article  CAS  Google Scholar 

  26. Barnidge DR, Dratz EA, Martin T, Bonilla LE, Moran LB, Lindall A (2003) Anal Chem 75:445–451

    Article  CAS  Google Scholar 

  27. DeKeyser SS, Li L (2006) Analyst 131:281–290

    Article  CAS  Google Scholar 

  28. O’Farrell PH (1975) J Biol Chem 250:4007–4021

    CAS  Google Scholar 

  29. Klose J, Kobalz U (1995) Electrophoresis 16:1034–1059

    Article  CAS  Google Scholar 

  30. Kahn P (1995) Science 270:369–370

    Article  CAS  Google Scholar 

  31. Fliser D, Novak J, Thongboonkerd V, Argiles A, Jankowski V, Girolami M, Jankowski J, Mischak H (2007) J Am Soc Nephrol 18:1057–1071

    Article  CAS  Google Scholar 

  32. Issaq HJ (2001) Electrophoresis 22:3629–3638

    Article  CAS  Google Scholar 

  33. Aebersold R, Goodlett DR (2001) Chem Rev 101:269–295

    Article  CAS  Google Scholar 

  34. Yanagida M (2002) J Chromatogr B Analyt Technol Biomed Life Sci 771:89–106

    Article  CAS  Google Scholar 

  35. Morrison RS, Kinoshita Y, Johnson MD, Uo T, Ho JT, McBee JK, Conrads TP, Veenstra TD (2002) Mol Cell Proteomics 1:553–560

    Article  CAS  Google Scholar 

  36. Sharma K, Lee S, Han S, Lee S, Francos B, McCue P, Wassell R, Shaw MA, RamachandraRao SP (2005) Proteomics 5:2648–2655

    Article  CAS  Google Scholar 

  37. Varghese SA, Powell TB, Budisavljevic MN, Oates JC, Raymond JR, Almeida JS, Arthur JM (2007) J Am Soc Nephrol 18:913–922

    Article  CAS  Google Scholar 

  38. Rao PV, Lu X, Standley M, Pattee P, Neelima G, Girisesh G, Dakshinamurthy KV, Roberts CT Jr, Nagalla SR (2007) Diabetes Care 30:629–637

    Article  CAS  Google Scholar 

  39. Pieper R, Gatlin CL, McGrath AM, Makusky AJ, Mondal M, Seonarain M, Field E, Schatz CR, Estock MA, Ahmed N, Anderson NG, Steiner S (2004) Proteomics 4:1159–1174

    Article  CAS  Google Scholar 

  40. Orenes-Pinero E, Corton M, Gonzalez-Peramato P, Algaba F, Casal I, Serrano A, Sanchez-Carbayo M (2007) J Proteome Res 6:4440–4448

    Article  CAS  Google Scholar 

  41. Link AJ, Eng J, Schieltz DM, Carmack E, Mize GJ, Morris DR, Garvik BM, Yates JR III (1999) Nat Biotechnol 17:676–682

    Article  CAS  Google Scholar 

  42. Delahunty CM, Yates JR III (2007) Biotechniques 43:563, 565, 567

    Article  Google Scholar 

  43. Cutillas PR, Norden AG, Cramer R, Burlingame AL, Unwin RJ (2003) Clin Sci (Lond) 104:483–490

    CAS  Google Scholar 

  44. Kreunin P, Zhao J, Rosser C, Urquidi V, Lubman DM, Goodison S (2007) J Proteome Res 6:2631–2639

    Article  CAS  Google Scholar 

  45. Shiwa M, Nishimura Y, Wakatabe R, Fukawa A, Arikuni H, Ota H, Kato Y, Yamori T (2003) Biochem Biophys Res Commun 309:18–25

    Article  CAS  Google Scholar 

  46. Woroniecki RP, Orlova TN, Mendelev N, Shatat IF, Hailpern SM, Kaskel FJ, Goligorsky MS, O’Riordan E (2006) Am J Nephrol 26:258–267

    Article  CAS  Google Scholar 

  47. Schaub S, Rush D, Wilkins J, Gibson IW, Weiler T, Sangster K, Nicolle L, Karpinski M, Jeffery J, Nickerson P (2004) J Am Soc Nephrol 15:219–227

    Article  CAS  Google Scholar 

  48. Jahnukainen T, Malehorn D, Sun M, Lyons-Weiler J, Bigbee W, Gupta G, Shapiro R, Randhawa PS, Pelikan R, Hauskrecht M, Vats A (2006) J Am Soc Nephrol 17:3248–3256

    Article  CAS  Google Scholar 

  49. McLerran D, Grizzle WE, Feng Z, Thompson IM, Bigbee WL, Cazares LH, Chan DW, Dahlgren J, Diaz J, Kagan J, Lin DW, Malik G, Oelschlager D, Partin A, Randolph TW, Sokoll L, Srivastava S, Srivastava S, Thornquist M, Troyer D, Wright GL, Zhang Z, Zhu L, Semmes OJ (2008) Clin Chem 54:53–60

    Article  CAS  Google Scholar 

  50. Kolch W, Neususs C, Pelzing M, Mischak H (2005) Mass Spectrom Rev 24:959–977

    Article  CAS  Google Scholar 

  51. Simo C, Elvira C, Gonzalez N, San Roman J, Barbas C, Cifuentes A (2004) Electrophoresis 25:2056–2064

    Article  CAS  Google Scholar 

  52. Ullsten S, Zuberovic A, Wetterhall M, Hardenborg E, Markides KE, Bergquist J (2004) Electrophoresis 25:2090–2099

    Article  CAS  Google Scholar 

  53. Erny GL, Elvira C, San RJ, Cifuentes A (2006) Electrophoresis 27:1041–1049

    Article  CAS  Google Scholar 

  54. Garza S, Chang S, Moini M (2007) J Chromatogr A 1159:14–21

    Article  CAS  Google Scholar 

  55. Gaspar A, Englmann M, Fekete A, Harir M, Schmitt-Kopplin P (2008) Electrophoresis 29:66–79

    Article  CAS  Google Scholar 

  56. Ye B, Skates S, Mok SC, Horick NK, Rosenberg HF, Vitonis A, Edwards D, Sluss P, Han WK, Berkowitz RS, Cramer DW (2006) Clin Cancer Res 12:432–441

    Article  CAS  Google Scholar 

  57. Kasicka V (2008) Electrophoresis 29:179–206

    Article  CAS  Google Scholar 

  58. Abdi H (2007) Bonferroni and Sidak corrections for multiple comparisons. Sage, Thousand Oaks (CA)

    Google Scholar 

  59. Westfall PH, Young SS (1993) Resampling-based multiple testing: examples and methods for P-value adjustment. Wiley, New York

    Google Scholar 

  60. Villanueva J, Shaffer DR, Philip J, Chaparro CA, Erdjument-Bromage H, Olshen AB, Fleisher M, Lilja H, Brogi E, Boyd J, Sanchez-Carbayo M, Holland EC, Cordon-Cardo C, Scher HI, Tempst P (2006) J Clin Invest 116:271–284

    Article  CAS  Google Scholar 

  61. Baggerman G, Verleyen P, Clynen E, Huybrechts J, De LA, Schoofs L (2004) J Chromatogr B Analyt Technol Biomed Life Sci 803:3–16

    Article  CAS  Google Scholar 

  62. Ruggenenti P, Schieppati A, Remuzzi G (2001) Lancet 357:1601–1608

    Article  CAS  Google Scholar 

  63. Rossing P (2005) Diabetologia 48:1439–1444

    Article  CAS  Google Scholar 

  64. Wittke S, Fliser D, Haubitz M, Bartel S, Krebs R, Hausadel F, Hillmann M, Golovko I, Koester P, Haller H, Kaiser T, Mischak H, Weissinger EM (2003) J Chromatogr A 1013:173–181

    Article  CAS  Google Scholar 

  65. Weissinger EM, Wittke S, Kaiser T, Haller H, Bartel S, Krebs R, Golovko I, Rupprecht HD, Haubitz M, Hecker H, Mischak H, Fliser D (2004) Kidney Int 65:2426–2434

    Article  CAS  Google Scholar 

  66. Neuhoff N, Kaiser T, Wittke S, Krebs R, Pitt A, Burchard A, Sundmacher A, Schlegelberger B, Kolch W, Mischak H (2004) Rapid Commun Mass Spectrom 18:149–156

    Article  CAS  Google Scholar 

  67. Haubitz M, Wittke S, Weissinger EM, Walden M, Rupprecht HD, Floege J, Haller H, Mischak H (2005) Kidney Int 67:2313–2320

    Article  CAS  Google Scholar 

  68. Haubitz M, Fliser D, Rupprecht H, Floege J, Haller H, Rossing K, Walden M, Wittke S, Mischak H (2005) Nephrol Dial Transplant 20:V20

    Article  Google Scholar 

  69. Julian BA, Wittke S, Novak J, Good DM, Coon JJ, Kellmann M, Zurbig P, Schiffer E, Haubitz M, Moldoveanu Z, Calcatera SM, Wyatt RJ, Sykora J, Sladkova E, Hes O, Mischak H, McGuire BM (2007) Electrophoresis 28:4469–4483

    Article  CAS  Google Scholar 

  70. Mischak H, Kaiser T, Walden M, Hillmann M, Wittke S, Herrmann A, Knueppel S, Haller H, Fliser D (2004) Clin Sci (Lond) 107:485–495

    Article  CAS  Google Scholar 

  71. Meier M, Kaiser T, Herrmann A, Knueppel S, Hillmann M, Koester P, Danne T, Haller H, Fliser D, Mischak H (2005) J Diabetes Complications 19:223–232

    Article  Google Scholar 

  72. Rossing K, Mischak H, Dakna M, Zurbig P, Novak J, Julian BA, Good DM, Coon JJ, Tarnow L, Rossing P (2008) J Am Soc Nephrol (in press)

  73. Chevalier RL (2006) Nat Clin Pract Nephrol 2:157–168

    Article  CAS  Google Scholar 

  74. Decramer S, Wittke S, Mischak H, Zurbig P, Walden M, Bouissou F, Bascands JL, Schanstra JP (2006) Nat Med 12:398–400

    Article  CAS  Google Scholar 

  75. Thongboonkerd V, Malasit P (2005) Proteomics 5:1033–1042

    Article  CAS  Google Scholar 

  76. Goerner M, Gooley T, Flowers ME, Sullivan KM, Kiem HP, Sanders JE, Martin PJ, Storb R (2002) Biol Blood Marrow Transplant 8:47–56

    Article  CAS  Google Scholar 

  77. Kaiser T, Kamal H, Rank A, Kolb HJ, Holler E, Ganser A, Hertenstein B, Mischak H, Weissinger EM (2004) Blood 104:340–349

    Article  CAS  Google Scholar 

  78. Weissinger EM, Schiffer E, Hertenstein B, Ferrara JL, Holler E, Stadler M, Kolb HJ, Zander A, Zurbig P, Kellmann M, Ganser A (2007) Blood 109:5511–5519

    Article  CAS  Google Scholar 

  79. Zimmerli LU, Schiffer E, Zurbig P, Kellmann M, Mouls L, Pitt A, Coon JJ, Schmiederer RE, Mischak H, Peter K, Kolch W, Delles C, Dominiczak AF (2008) Mol Cell Proteomics 7:290–298

    CAS  Google Scholar 

  80. Dabelea D, Kinney G, Snell-Bergeon JK, Hokanson JE, Eckel RH, Ehrlich J, Garg S, Hamman RF, Rewers M (2003) Diabetes 52:2833–2839

    Article  CAS  Google Scholar 

  81. Rossing K, Mischak H, Parving HH, Christensen PK, Walden M, Hillmann M, Kaiser T (2005) Kidney Int 68:193–205

    Article  CAS  Google Scholar 

  82. Wittke S, Haubitz M, Walden M, Rohde F, Schwarz A, Mengel M, Mischak H, Haller H, Gwinner W (2005) Am J Transplant 5:2479–2488

    Article  CAS  Google Scholar 

  83. Comper WD, Osicka TM, Clark M, MacIsaac RJ, Jerums G (2004) Kidney Int 65:1850–1855

    Article  CAS  Google Scholar 

  84. Nemirovskiy OV, Dufield DR, Sunyer T, Aggarwal P, Welsch DJ, Mathews WR (2007) Anal Biochem 369:41–53

    Article  CAS  Google Scholar 

  85. Cooper ME, Cao Z, Rumble JR, Jandeleit K, Allen TJ, Gilbert RE (1998) Metabolism 47:24–27

    Article  CAS  Google Scholar 

  86. Rossing K, Mischak H, Rossing P, Schanstra JP, Wiseman A, Maahs DM (2008) Proteomics Clin Appl (in press)

  87. Candiano G, Musante L, Bruschi M, Petretto A, Santucci L, Del BP, Pavone B, Perfumo F, Urbani A, Scolari F, Ghiggeri GM (2006) J Am Soc Nephrol 17:3139–3148

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Mosaiques diagnostics & therapeutics, Mellendorfer Str. 7–9, 30625, Hannover, Germany

    Jochen Metzger & Harald Mischak

  2. Department of Renal and Cardiac Remodelling, Inserm, U858/I2MR, Team #5, 1 Avenue Jean Poulhès, BP 84225, 31432, Toulouse Cedex 4, France

    Joost P. Schanstra

  3. Institut de Médecine Moléculaire de Rangueil, Université Toulouse III Paul Sabatier, 31000, Toulouse, France

    Joost P. Schanstra

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  1. Jochen Metzger
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Metzger, J., Schanstra, J.P. & Mischak, H. Capillary electrophoresis–mass spectrometry in urinary proteome analysis: current applications and future developments. Anal Bioanal Chem 393, 1431–1442 (2009). https://doi.org/10.1007/s00216-008-2309-0

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