Advertisement

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

  • Jochen MetzgerEmail author
  • Joost P. Schanstra
  • Harald Mischak
Review

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.

Keywords

Biomarker discovery Capillary electrophoresis–mass spectrometry Urinary proteome analysis 

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. 1.
    Goodsaid F, Bandow JE, Mischak H (2007) Proteomics Clin Appl 1:1526–1531CrossRefGoogle Scholar
  2. 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 1:148–156CrossRefGoogle Scholar
  3. 3.
    deVera IE, Katz JE, Agus DB (2006) Clin Adv Hematol Oncol 4:541–549Google Scholar
  4. 4.
    Good DM, Thongboonkerd V, Novak J, Bascands JL, Schanstra JP, Coon JJ, Dominiczak A, Mischak H (2007) J Proteome Res 6:4549–4555CrossRefGoogle Scholar
  5. 5.
    Lescuyer P, Hochstrasser D, Rabilloud T (2007) J Proteome Res 6:3371–3376CrossRefGoogle Scholar
  6. 6.
    Rai AJ (2007) Expert Rev Mol Diagn 7:545–553CrossRefGoogle Scholar
  7. 7.
    Wuhrer M (2007) Expert Rev Proteomics 4:135–136CrossRefGoogle Scholar
  8. 8.
    Tomana M, Novak J, Julian BA, Matousovic K, Konecny K, Mestecky J (1999) J Clin Invest 104:73–81CrossRefGoogle Scholar
  9. 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 280:19136–19145CrossRefGoogle Scholar
  10. 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 71:1148–1154CrossRefGoogle Scholar
  11. 11.
    Schaub S, Wilkins J, Weiler T, Sangster K, Rush D, Nickerson P (2004) Kidney Int 65:323–332CrossRefGoogle Scholar
  12. 12.
    Theodorescu D, Wittke S, Ross MM, Walden M, Conaway M, Just I, Mischak H, Frierson HF (2006) Lancet Oncol 7:230–240CrossRefGoogle Scholar
  13. 13.
    Vestergaard P, Leverett R (1958) J Lab Clin Med 51:211–218Google Scholar
  14. 14.
    Schiffer E, Mischak H, Novak J (2006) Proteomics 6:5615–5627CrossRefGoogle Scholar
  15. 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)Google Scholar
  16. 16.
    Yamamoto T, Langham RG, Ronco P, Knepper MA, Thongboonkerd V (2008) Proteomics 8:2156–2159CrossRefGoogle Scholar
  17. 17.
    Thongboonkerd V (2007) J Proteome Res 6:3881–3890CrossRefGoogle Scholar
  18. 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 2:556–570CrossRefGoogle Scholar
  19. 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 26:2797–2808CrossRefGoogle Scholar
  20. 20.
    Mischak H, Julian BA, Novak J (2007) Proteomics Clin Appl 1:792–804CrossRefGoogle Scholar
  21. 21.
    Thongboonkerd V (2007) Proteomics Clin Appl 1:780–791CrossRefGoogle Scholar
  22. 22.
    Bons JA, de BD, van Dieijen-Visser MP, Wodzig WK (2006) Clin Chim Acta 366:249–256CrossRefGoogle Scholar
  23. 23.
    Righetti PG, Campostrini N, Pascali J, Hamdan M, Astner H (2004) Eur J Mass Spectrom (Chichester, Eng) 10:335–348CrossRefGoogle Scholar
  24. 24.
    Ong SE, Mann M (2005) Nat Chem Biol 1:252–262CrossRefGoogle Scholar
  25. 25.
    Zybailov B, Coleman MK, Florens L, Washburn MP (2005) Anal Chem 77:6218–6224CrossRefGoogle Scholar
  26. 26.
    Barnidge DR, Dratz EA, Martin T, Bonilla LE, Moran LB, Lindall A (2003) Anal Chem 75:445–451CrossRefGoogle Scholar
  27. 27.
    DeKeyser SS, Li L (2006) Analyst 131:281–290CrossRefGoogle Scholar
  28. 28.
    O’Farrell PH (1975) J Biol Chem 250:4007–4021Google Scholar
  29. 29.
    Klose J, Kobalz U (1995) Electrophoresis 16:1034–1059CrossRefGoogle Scholar
  30. 30.
    Kahn P (1995) Science 270:369–370CrossRefGoogle Scholar
  31. 31.
    Fliser D, Novak J, Thongboonkerd V, Argiles A, Jankowski V, Girolami M, Jankowski J, Mischak H (2007) J Am Soc Nephrol 18:1057–1071CrossRefGoogle Scholar
  32. 32.
    Issaq HJ (2001) Electrophoresis 22:3629–3638CrossRefGoogle Scholar
  33. 33.
    Aebersold R, Goodlett DR (2001) Chem Rev 101:269–295CrossRefGoogle Scholar
  34. 34.
    Yanagida M (2002) J Chromatogr B Analyt Technol Biomed Life Sci 771:89–106CrossRefGoogle Scholar
  35. 35.
    Morrison RS, Kinoshita Y, Johnson MD, Uo T, Ho JT, McBee JK, Conrads TP, Veenstra TD (2002) Mol Cell Proteomics 1:553–560CrossRefGoogle Scholar
  36. 36.
    Sharma K, Lee S, Han S, Lee S, Francos B, McCue P, Wassell R, Shaw MA, RamachandraRao SP (2005) Proteomics 5:2648–2655CrossRefGoogle Scholar
  37. 37.
    Varghese SA, Powell TB, Budisavljevic MN, Oates JC, Raymond JR, Almeida JS, Arthur JM (2007) J Am Soc Nephrol 18:913–922CrossRefGoogle Scholar
  38. 38.
    Rao PV, Lu X, Standley M, Pattee P, Neelima G, Girisesh G, Dakshinamurthy KV, Roberts CT Jr, Nagalla SR (2007) Diabetes Care 30:629–637CrossRefGoogle Scholar
  39. 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 4:1159–1174CrossRefGoogle Scholar
  40. 40.
    Orenes-Pinero E, Corton M, Gonzalez-Peramato P, Algaba F, Casal I, Serrano A, Sanchez-Carbayo M (2007) J Proteome Res 6:4440–4448CrossRefGoogle Scholar
  41. 41.
    Link AJ, Eng J, Schieltz DM, Carmack E, Mize GJ, Morris DR, Garvik BM, Yates JR III (1999) Nat Biotechnol 17:676–682CrossRefGoogle Scholar
  42. 42.
    Delahunty CM, Yates JR III (2007) Biotechniques 43:563, 565, 567CrossRefGoogle Scholar
  43. 43.
    Cutillas PR, Norden AG, Cramer R, Burlingame AL, Unwin RJ (2003) Clin Sci (Lond) 104:483–490Google Scholar
  44. 44.
    Kreunin P, Zhao J, Rosser C, Urquidi V, Lubman DM, Goodison S (2007) J Proteome Res 6:2631–2639CrossRefGoogle Scholar
  45. 45.
    Shiwa M, Nishimura Y, Wakatabe R, Fukawa A, Arikuni H, Ota H, Kato Y, Yamori T (2003) Biochem Biophys Res Commun 309:18–25CrossRefGoogle Scholar
  46. 46.
    Woroniecki RP, Orlova TN, Mendelev N, Shatat IF, Hailpern SM, Kaskel FJ, Goligorsky MS, O’Riordan E (2006) Am J Nephrol 26:258–267CrossRefGoogle Scholar
  47. 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 15:219–227CrossRefGoogle Scholar
  48. 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 17:3248–3256CrossRefGoogle Scholar
  49. 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 54:53–60CrossRefGoogle Scholar
  50. 50.
    Kolch W, Neususs C, Pelzing M, Mischak H (2005) Mass Spectrom Rev 24:959–977CrossRefGoogle Scholar
  51. 51.
    Simo C, Elvira C, Gonzalez N, San Roman J, Barbas C, Cifuentes A (2004) Electrophoresis 25:2056–2064CrossRefGoogle Scholar
  52. 52.
    Ullsten S, Zuberovic A, Wetterhall M, Hardenborg E, Markides KE, Bergquist J (2004) Electrophoresis 25:2090–2099CrossRefGoogle Scholar
  53. 53.
    Erny GL, Elvira C, San RJ, Cifuentes A (2006) Electrophoresis 27:1041–1049CrossRefGoogle Scholar
  54. 54.
    Garza S, Chang S, Moini M (2007) J Chromatogr A 1159:14–21CrossRefGoogle Scholar
  55. 55.
    Gaspar A, Englmann M, Fekete A, Harir M, Schmitt-Kopplin P (2008) Electrophoresis 29:66–79CrossRefGoogle Scholar
  56. 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 12:432–441CrossRefGoogle Scholar
  57. 57.
    Kasicka V (2008) Electrophoresis 29:179–206CrossRefGoogle Scholar
  58. 58.
    Abdi H (2007) Bonferroni and Sidak corrections for multiple comparisons. Sage, Thousand Oaks (CA)Google Scholar
  59. 59.
    Westfall PH, Young SS (1993) Resampling-based multiple testing: examples and methods for P-value adjustment. Wiley, New YorkGoogle Scholar
  60. 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 116:271–284CrossRefGoogle Scholar
  61. 61.
    Baggerman G, Verleyen P, Clynen E, Huybrechts J, De LA, Schoofs L (2004) J Chromatogr B Analyt Technol Biomed Life Sci 803:3–16CrossRefGoogle Scholar
  62. 62.
    Ruggenenti P, Schieppati A, Remuzzi G (2001) Lancet 357:1601–1608CrossRefGoogle Scholar
  63. 63.
    Rossing P (2005) Diabetologia 48:1439–1444CrossRefGoogle Scholar
  64. 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 1013:173–181CrossRefGoogle Scholar
  65. 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 65:2426–2434CrossRefGoogle Scholar
  66. 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 18:149–156CrossRefGoogle Scholar
  67. 67.
    Haubitz M, Wittke S, Weissinger EM, Walden M, Rupprecht HD, Floege J, Haller H, Mischak H (2005) Kidney Int 67:2313–2320CrossRefGoogle Scholar
  68. 68.
    Haubitz M, Fliser D, Rupprecht H, Floege J, Haller H, Rossing K, Walden M, Wittke S, Mischak H (2005) Nephrol Dial Transplant 20:V20CrossRefGoogle Scholar
  69. 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 28:4469–4483CrossRefGoogle Scholar
  70. 70.
    Mischak H, Kaiser T, Walden M, Hillmann M, Wittke S, Herrmann A, Knueppel S, Haller H, Fliser D (2004) Clin Sci (Lond) 107:485–495CrossRefGoogle Scholar
  71. 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 19:223–232CrossRefGoogle Scholar
  72. 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)Google Scholar
  73. 73.
    Chevalier RL (2006) Nat Clin Pract Nephrol 2:157–168CrossRefGoogle Scholar
  74. 74.
    Decramer S, Wittke S, Mischak H, Zurbig P, Walden M, Bouissou F, Bascands JL, Schanstra JP (2006) Nat Med 12:398–400CrossRefGoogle Scholar
  75. 75.
    Thongboonkerd V, Malasit P (2005) Proteomics 5:1033–1042CrossRefGoogle Scholar
  76. 76.
    Goerner M, Gooley T, Flowers ME, Sullivan KM, Kiem HP, Sanders JE, Martin PJ, Storb R (2002) Biol Blood Marrow Transplant 8:47–56CrossRefGoogle Scholar
  77. 77.
    Kaiser T, Kamal H, Rank A, Kolb HJ, Holler E, Ganser A, Hertenstein B, Mischak H, Weissinger EM (2004) Blood 104:340–349CrossRefGoogle Scholar
  78. 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 109:5511–5519CrossRefGoogle Scholar
  79. 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 7:290–298Google Scholar
  80. 80.
    Dabelea D, Kinney G, Snell-Bergeon JK, Hokanson JE, Eckel RH, Ehrlich J, Garg S, Hamman RF, Rewers M (2003) Diabetes 52:2833–2839CrossRefGoogle Scholar
  81. 81.
    Rossing K, Mischak H, Parving HH, Christensen PK, Walden M, Hillmann M, Kaiser T (2005) Kidney Int 68:193–205CrossRefGoogle Scholar
  82. 82.
    Wittke S, Haubitz M, Walden M, Rohde F, Schwarz A, Mengel M, Mischak H, Haller H, Gwinner W (2005) Am J Transplant 5:2479–2488CrossRefGoogle Scholar
  83. 83.
    Comper WD, Osicka TM, Clark M, MacIsaac RJ, Jerums G (2004) Kidney Int 65:1850–1855CrossRefGoogle Scholar
  84. 84.
    Nemirovskiy OV, Dufield DR, Sunyer T, Aggarwal P, Welsch DJ, Mathews WR (2007) Anal Biochem 369:41–53CrossRefGoogle Scholar
  85. 85.
    Cooper ME, Cao Z, Rumble JR, Jandeleit K, Allen TJ, Gilbert RE (1998) Metabolism 47:24–27CrossRefGoogle Scholar
  86. 86.
    Rossing K, Mischak H, Rossing P, Schanstra JP, Wiseman A, Maahs DM (2008) Proteomics Clin Appl (in press)Google Scholar
  87. 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 17:3139–3148CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Jochen Metzger
    • 1
    Email author
  • Joost P. Schanstra
    • 2
    • 3
  • Harald Mischak
    • 1
  1. 1.Mosaiques diagnostics & therapeuticsHannoverGermany
  2. 2.Department of Renal and Cardiac RemodellingInserm, U858/I2MR, Team #5Toulouse Cedex 4France
  3. 3.Institut de Médecine Moléculaire de RangueilUniversité Toulouse III Paul SabatierToulouseFrance

Personalised recommendations