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Biological Sample Collection for Clinical Proteomics: Existing SOPs

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Clinical Proteomics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1243))

Abstract

Proteomic study of clinical samples aims at the better understanding of physiological and pathological conditions, as well as the discovery of diagnostic and prognostic markers for the latter. Quantitative and/or qualitative variations of body fluid proteome may reflect health- or disease-associated events connected to the adjacent or distant body regions of the fluid production/secretion/excretion and/or systemic reactions to the presence of disease. Sample collection and preparation is a critical step in order to obtain useful and valid information in clinical proteomics analysis. In this chapter, we present the current protocols and guidelines for human body fluid collection and storage, prior to proteomic analysis. A variety of body fluids that are currently being used in proteomic analysis and have potential interest in clinical practice are presented including blood plasma and serum, urine, cerebrospinal fluid, cerumen, nasal secretions, saliva, tears, breast milk, bronchoalveolar fluid, nipple aspirate fluid, amniotic fluid, bile, cervico-vaginal fluid, and seminal plasma. With no doubt these body fluids differ in the extent of their application in clinical proteomics investigations, hence in some cases the presented SOPs are established following more extensive testing (e.g., plasma, serum, urine, CSF) than others (nasal secretions, saliva, tears, breast milk, bronchoalveolar fluid, nipple aspirate fluid, amniotic fluid, bile, cervico-vaginal fluid, and seminal plasma). However, even in these latter cases, the presented protocols were reported by at least two independent groups according to the literature. We hope they can thus serve as a reliable guide for sample collection based on our current knowledge in the field and excellent starting points for proteomics investigators. It should also be pointed that variations to these protocols exist and their further refinement in the future is foreseen following the evolution of the proteomics technologies.

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References

  1. American Red Cross. Plasma. Available from http://www.redcrossblood.org/learn-about-blood/blood-components/plasma

  2. Omenn GS, Menon R, Adamski M, Blackwell T, Haab BB, Gao W, States DJ (2007) The human plasma and serum proteome. In: Thongboonkerd V (ed) Proteomics of human body fluids. Humana, Totowa

    Google Scholar 

  3. Schulte I, Tammen H, Selle H et al (2005) Peptides in body fluids and tissues as markers of disease. Expert Rev Mol Diagn 5:145–157

    Article  CAS  PubMed  Google Scholar 

  4. Granger J, Siddiqui J, Copeland S et al (2005) Albumin depletion of human plasma also removes low abundance proteins including the cytokines. Proteomics 5:4713–4718

    Article  CAS  PubMed  Google Scholar 

  5. Guerrier L, Righetti PG, Boschetti E (2008) Reduction of dynamic protein concentration range of biological extracts for the discovery of low-abundance proteins by means of hexapeptide ligand library. Nat Protoc 3:883–890

    Article  CAS  PubMed  Google Scholar 

  6. Bodzon-Kulakowska A, Bierczynska-Krzysik A, Dylag T et al (2007) Methods for samples preparation in proteomic research. J Chromatogr B Analyt Technol Biomed Life Sci 849:1–31

    Article  CAS  PubMed  Google Scholar 

  7. Omenn GS (2007) THE HUPO human plasma proteome project. Proteomics Clin Appl 1:769–779

    Article  CAS  PubMed  Google Scholar 

  8. Muthusamy B, Hanumanthu G, Suresh S et al (2005) Plasma Proteome Database as a resource for proteomics research. Proteomics 5:3531–3536

    Article  CAS  PubMed  Google Scholar 

  9. Plasma Proteome Database. Available from http://www.plasmaproteomedatabase.org/index.html

  10. Rai AJ, Gelfand CA, Haywood BC et al (2005) HUPO Plasma Proteome Project specimen collection and handling: towards the standardization of parameters for plasma proteome samples. Proteomics 5:3262–3277

    Article  CAS  PubMed  Google Scholar 

  11. Kim MR, Kim CW (2007) Human blood plasma preparation for two-dimensional gel electrophoresis. J Chromatogr B Analyt Technol Biomed Life Sci 849:203–210

    Article  CAS  PubMed  Google Scholar 

  12. Di Domenico M, Scumaci D, Grasso S et al (2013) Biomarker discovery by plasma proteomics in familial Brugada Syndrome. Front Biosci (Landmark Ed) 18:564–571

    Article  Google Scholar 

  13. Tammen H (2008) Specimen collection and handling: standardization of blood sample collection. Methods Mol Biol 428:35–42

    Article  PubMed  Google Scholar 

  14. Issaq HJ, Xiao Z, Veenstra TD (2007) Serum and plasma proteomics. Chem Rev 107:3601–3620

    Article  CAS  PubMed  Google Scholar 

  15. Adkins JN, Varnum SM, Auberry KJ et al (2002) Toward a human blood serum proteome: analysis by multidimensional separation coupled with mass spectrometry. Mol Cell Proteomics 1:947–955

    Article  CAS  PubMed  Google Scholar 

  16. Putnam DF (1971) Composition and concentrative properties of human urine. National Aeronautics and Space Administration, Washington

    Google Scholar 

  17. Rodriguez-Suarez E, Siwy J, Zurbig P et al (2013) Urine as a source for clinical proteome analysis: from discovery to clinical application. Biochim Biophys Acta 1844(5):884–898

    Article  PubMed  Google Scholar 

  18. Mischak H, Kolch W, Aivaliotis M et al (2010) Comprehensive human urine standards for comparability and standardization in clinical proteome analysis. Proteomics Clin Appl 4:464–478

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Yamamoto T (2010) The 4th Human Kidney and Urine Proteome Project (HKUPP) workshop. 26 September 2009, Toronto, Canada. Proteomics 10:2069–2070

    Article  CAS  PubMed  Google Scholar 

  20. Yamamoto T, Langham RG, Ronco P et al (2008) Towards standard protocols and guidelines for urine proteomics: a report on the Human Kidney and Urine Proteome Project (HKUPP) symposium and workshop, 6 October 2007, Seoul, Korea and 1 November 2007, San Francisco, CA, USA. Proteomics 8:2156–2159

    Article  CAS  PubMed  Google Scholar 

  21. Zurbig P, Dihazi H, Metzger J et al (2011) Urine proteomics in kidney and urogenital diseases: moving towards clinical applications. Proteomics Clin Appl 5:256–268

    Article  PubMed  Google Scholar 

  22. van Gool AJ, Hendrickson RC (2012) The proteomic toolbox for studying cerebrospinal fluid. Expert Rev Proteomics 9:165–179

    Article  PubMed  Google Scholar 

  23. Ramström M, Bergquist J (2007) The human plasma and serum proteome. In: Thongboonkerd V (ed) Proteomics of human body fluids. Humana, Totowa

    Google Scholar 

  24. Kroksveen AC, Opsahl JA, Aye TT et al (2011) Proteomics of human cerebrospinal fluid: discovery and verification of biomarker candidates in neurodegenerative diseases using quantitative proteomics. J Proteomics 74:371–388

    Article  CAS  PubMed  Google Scholar 

  25. Teunissen CE, Petzold A, Bennett JL et al (2009) A consensus protocol for the standardization of cerebrospinal fluid collection and biobanking. Neurology 73:1914–1922

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Casado B, Pannell LK, Iadarola P et al (2005) Identification of human nasal mucous proteins using proteomics. Proteomics 5:2949–2959

    Article  CAS  PubMed  Google Scholar 

  27. Casado B, Viglio S, Baraniuk JN (2007) Proteomics of sinusitis nasal lavage fluid. In: Thongboonkerd V (ed) Proteomics of human body fluids. Humana, Totowa

    Google Scholar 

  28. Casado B, Iadarola P, Pannell L (2008) Preparation of nasal secretions for proteome analysis. In: Posch A (ed) 2D PAGE: sample preparation and fractionation. Humana, Totowa, pp 77–87

    Google Scholar 

  29. Caseiro A, Ferreira R, Padrao A et al (2013) Salivary proteome and peptidome profiling in type 1 diabetes mellitus using a quantitative approach. J Proteome Res 12(4):1700–1709

    Article  CAS  PubMed  Google Scholar 

  30. Casado B, Iadarola P, Pannell LK (2008) Preparation of nasal secretions for proteome analysis. Methods Mol Biol 425:77–87

    Article  CAS  PubMed  Google Scholar 

  31. Lamy E, Mau M (2012) Saliva proteomics as an emerging, non-invasive tool to study livestock physiology, nutrition and diseases. J Proteomics 75:4251–4258

    Article  CAS  PubMed  Google Scholar 

  32. Vitorino R, Guedes S, Manadas B et al (2012) Toward a standardized saliva proteome analysis methodology. J Proteomics 75:5140–5165

    Article  CAS  PubMed  Google Scholar 

  33. He H, Sun G, Ping F et al (2011) A new and preliminary three-dimensional perspective: proteomes of optimization between OSCC and OLK. Artif Cells Blood Substit Immobil Biotechnol 39:26–30

    Article  CAS  PubMed  Google Scholar 

  34. Goncalves Lda R, Soares MR, Nogueira FC et al (2010) Comparative proteomic analysis of whole saliva from chronic periodontitis patients. J Proteomics 73:1334–1341

    Article  PubMed  Google Scholar 

  35. Rudney JD, Staikov RK, Johnson JD (2009) Potential biomarkers of human salivary function: a modified proteomic approach. Arch Oral Biol 54:91–100

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Vitorino R, de Morais Guedes S, Ferreira R et al (2006) Two-dimensional electrophoresis study of in vitro pellicle formation and dental caries susceptibility. Eur J Oral Sci 114:147–153

    Article  CAS  PubMed  Google Scholar 

  37. Cabras T, Pisano E, Mastinu A et al (2010) Alterations of the salivary secretory peptidome profile in children affected by type 1 diabetes. Mol Cell Proteomics 9:2099–2108

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Hu S, Wang J, Meijer J et al (2007) Salivary proteomic and genomic biomarkers for primary Sjogren’s syndrome. Arthritis Rheum 56:3588–3600

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Ambatipudi KS, Swatkoski S, Moresco JJ et al (2012) Quantitative proteomics of parotid saliva in primary Sjogren’s syndrome. Proteomics 12:3113–3120

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Wu ZZ, Wang JG, Zhang XL (2009) Diagnostic model of saliva protein finger print analysis of patients with gastric cancer. World J Gastroenterol 15:865–870

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Jarai T, Maasz G, Burian A et al (2012) Mass spectrometry-based salivary proteomics for the discovery of head and neck squamous cell carcinoma. Pathol Oncol Res 18:623–628

    Article  CAS  PubMed  Google Scholar 

  42. Dowling P, Wormald R, Meleady P et al (2008) Analysis of the saliva proteome from patients with head and neck squamous cell carcinoma reveals differences in abundance levels of proteins associated with tumour progression and metastasis. J Proteomics 71:168–175

    Article  CAS  PubMed  Google Scholar 

  43. Xiao H, Zhang L, Zhou H et al (2012) Proteomic analysis of human saliva from lung cancer patients using two-dimensional difference gel electrophoresis and mass spectrometry. Mol Cell Proteomics 11(M111):012112

    PubMed  Google Scholar 

  44. WHO (2007) Common minimum technical standards and protocols for biological resource centres dedicated to cancer research. International Agency for Research on Cancer, Working Group Reports. vol. 2

    Google Scholar 

  45. Vitorino R, Barros AS, Caseiro A et al (2012) Evaluation of different extraction procedures for salivary peptide analysis. Talanta 94:209–215

    Article  CAS  PubMed  Google Scholar 

  46. Ananthi S, Santhosh RS, Nila MV et al (2011) Comparative proteomics of human male and female tears by two-dimensional electrophoresis. Exp Eye Res 92:454–463

    Article  CAS  PubMed  Google Scholar 

  47. Saijyothi AV, Angayarkanni N, Syama C et al (2010) Two dimensional electrophoretic analysis of human tears: collection method in dry eye syndrome. Electrophoresis 31:3420–3427

    Article  CAS  PubMed  Google Scholar 

  48. Zhou L, Beuerman RW, Chan CM et al (2009) Identification of tear fluid biomarkers in dry eye syndrome using iTRAQ quantitative proteomics. J Proteome Res 8:4889–4905

    Article  CAS  PubMed  Google Scholar 

  49. Acera A, Rocha G, Vecino E et al (2008) Inflammatory markers in the tears of patients with ocular surface disease. Ophthalmic Res 40:315–321

    Article  CAS  PubMed  Google Scholar 

  50. Argueso P, Balaram M, Spurr-Michaud S et al (2002) Decreased levels of the goblet cell mucin MUC5AC in tears of patients with Sjogren syndrome. Invest Ophthalmol Vis Sci 43:1004–1011

    PubMed  Google Scholar 

  51. Saghizadeh M, Brown DJ, Castellon R et al (2001) Overexpression of matrix metalloproteinase-10 and matrix metalloproteinase-3 in human diabetic corneas: a possible mechanism of basement membrane and integrin alterations. Am J Pathol 158:723–734

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Wong TT, Zhou L, Li J et al (2011) Proteomic profiling of inflammatory signaling molecules in the tears of patients on chronic glaucoma medication. Invest Ophthalmol Vis Sci 52:7385–7391

    Article  CAS  PubMed  Google Scholar 

  53. Liao Y, Alvarado R, Phinney B et al (2011) Proteomic characterization of human milk whey proteins during a twelve-month lactation period. J Proteome Res 10:1746–1754

    Article  CAS  PubMed  Google Scholar 

  54. Conti A, Giuffrida MG, Cavaletto M (2007) Proteomics of human milk. In: Thongboonkerd V (ed) Proteomics of human body fluids. Humana, Totowa

    Google Scholar 

  55. Gao X, McMahon RJ, Woo JG et al (2012) Temporal changes in milk proteomes reveal developing milk functions. J Proteome Res 11:3897–3907

    Article  CAS  PubMed  Google Scholar 

  56. Dallas DC, Guerrero A, Khaldi N et al (2013) Extensive in vivo human milk peptidomics reveals specific proteolysis yielding protective antimicrobial peptides. J Proteome Res 12:2295–2304

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  57. Govender P, Dunn MJ, Donnelly SC (2009) Proteomics and the lung: analysis of bronchoalveolar lavage fluid. Proteomics Clin Appl 3:1044–1051

    Article  CAS  PubMed  Google Scholar 

  58. Foster MW, Thompson JW, Que LG et al (2013) Proteomic analysis of human bronchoalveolar lavage fluid after subsgemental exposure. J Proteome Res 12:2194–2205

    Article  CAS  PubMed  Google Scholar 

  59. Lee AS (2004) American Thoracic Society. Bronchoalveolar Lavage. Available from http://www.thoracic.org/clinical/critical-care/critical-care-procedures/bronchoalveolar-lavage.php

  60. Pastor MD, Nogal A, Molina-Pinelo S et al (2013) Identification of proteomic signatures associated with lung cancer and COPD. J Proteomics 89:227–237

    Article  CAS  PubMed  Google Scholar 

  61. Kosanam H, Sato M, Batruch I et al (2012) Differential proteomic analysis of bronchoalveolar lavage fluid from lung transplant patients with and without chronic graft dysfunction. Clin Biochem 45:223–230

    Article  CAS  PubMed  Google Scholar 

  62. Cederfur C, Malmstrom J, Nihlberg K et al (2012) Glycoproteomic identification of galectin-3 and -8 ligands in bronchoalveolar lavage of mild asthmatics and healthy subjects. Biochim Biophys Acta 1820:1429–1436

    Article  CAS  PubMed  Google Scholar 

  63. Ruhlen RL, Sauter ER (2007) Proteomics of nipple aspirate fluid, breast cyst fluid, milk, and colostrum. Proteomics Clin Appl 1:845–852

    Article  CAS  PubMed  Google Scholar 

  64. Ruhlen RL, Sauter ER (2007) Proteomic analysis of breast tissue and nipple aspirate fluid for breast cancer detection. Biomark Med 1:251–260

    Article  CAS  PubMed  Google Scholar 

  65. Pavlou MP, Kulasingam V, Sauter ER et al (2010) Nipple aspirate fluid proteome of healthy females and patients with breast cancer. Clin Chem 56:848–855

    Article  CAS  PubMed  Google Scholar 

  66. Pawlik TM, Hawke DH, Liu Y et al (2006) Proteomic analysis of nipple aspirate fluid from women with early-stage breast cancer using isotope-coded affinity tags and tandem mass spectrometry reveals differential expression of vitamin D binding protein. BMC Cancer 6:68

    Article  PubMed Central  PubMed  Google Scholar 

  67. Alexander H, Stegner AL, Wagner-Mann C et al (2004) Proteomic analysis to identify breast cancer biomarkers in nipple aspirate fluid. Clin Cancer Res 10:7500–7510

    Article  CAS  PubMed  Google Scholar 

  68. Noble J, Dua RS, Locke I et al (2007) Proteomic analysis of nipple aspirate fluid throughout the menstrual cycle in healthy pre-menopausal women. Breast Cancer Res Treat 104:191–196

    Article  CAS  PubMed  Google Scholar 

  69. Cho CK, Smith CR, Diamandis EP (2010) Amniotic fluid proteome analysis from Down syndrome pregnancies for biomarker discovery. J Proteome Res 9:3574–3582

    Article  CAS  PubMed  Google Scholar 

  70. Kolialexi A, Tounta G, Mavrou A et al (2011) Proteomic analysis of amniotic fluid for the diagnosis of fetal aneuploidies. Expert Rev Proteomics 8:175–185

    Article  CAS  PubMed  Google Scholar 

  71. Amniocentesis protocol (2011) Available from http://hsc.unm.edu/som/obgyn/docs/protocols/20.pdf

  72. Tsangaris GT, Kolialexi A, Karamessinis PM et al (2006) The normal human amniotic fluid supernatant proteome. In Vivo 20:479–490

    CAS  PubMed  Google Scholar 

  73. Cho CK, Shan SJ, Winsor EJ et al (2007) Proteomics analysis of human amniotic fluid. Mol Cell Proteomics 6:1406–1415

    Article  CAS  PubMed  Google Scholar 

  74. Barbhuiya MA, Sahasrabuddhe NA, Pinto SM et al (2011) Comprehensive proteomic analysis of human bile. Proteomics 11:4443–4453

    Article  CAS  PubMed  Google Scholar 

  75. Farina A, Dumonceau JM, Lescuyer P (2009) Proteomic analysis of human bile and potential applications for cancer diagnosis. Expert Rev Proteomics 6:285–301

    Article  CAS  PubMed  Google Scholar 

  76. Farina A, Dumonceau JM, Frossard JL et al (2009) Proteomic analysis of human bile from malignant biliary stenosis induced by pancreatic cancer. J Proteome Res 8:159–169

    Article  CAS  PubMed  Google Scholar 

  77. Tang LJ, De Seta F, Odreman F et al (2007) Proteomic analysis of human cervical-vaginal fluids. J Proteome Res 6:2874–2883

    Article  CAS  PubMed  Google Scholar 

  78. Shaw JL, Smith CR, Diamandis EP (2007) Proteomic analysis of human cervico-vaginal fluid. J Proteome Res 6:2859–2865

    Article  CAS  PubMed  Google Scholar 

  79. Lockwood CJ, Senyei AE, Dische MR et al (1991) Fetal fibronectin in cervical and vaginal secretions as a predictor of preterm delivery. N Engl J Med 325:669–674

    Article  CAS  PubMed  Google Scholar 

  80. Kalinka J, Sobala W, Wasiela M et al (2005) Decreased proinflammatory cytokines in cervicovaginal fluid, as measured in midgestation, are associated with preterm delivery. Am J Reprod Immunol 54:70–76

    Article  CAS  PubMed  Google Scholar 

  81. Dasari S, Pereira L, Reddy AP et al (2007) Comprehensive proteomic analysis of human cervical-vaginal fluid. J Proteome Res 6:1258–1268

    Article  CAS  PubMed  Google Scholar 

  82. Di Quinzio MK, Oliva K, Holdsworth SJ et al (2007) Proteomic analysis and characterisation of human cervico-vaginal fluid proteins. Aust N Z J Obstet Gynaecol 47:9–15

    Article  PubMed  Google Scholar 

  83. Pereira L, Reddy AP, Jacob T et al (2007) Identification of novel protein biomarkers of preterm birth in human cervical-vaginal fluid. J Proteome Res 6:1269–1276

    Article  CAS  PubMed  Google Scholar 

  84. Davalieva K, Kiprijanovska S, Noveski P et al (2012) Human seminal plasma proteome study: a search for male infertility biomarkers. Balkan J Med Genet 15:35–38

    CAS  PubMed Central  PubMed  Google Scholar 

  85. Milardi D, Grande G, Vincenzoni F et al (2012) Proteomic approach in the identification of fertility pattern in seminal plasma of fertile men. Fertil Steril 97:67–73 e61

    Article  CAS  PubMed  Google Scholar 

  86. Davalieva K, Kiprijanovska S, Noveski P et al (2012) Proteomic analysis of seminal plasma in men with different spermatogenic impairment. Andrologia 44:256–264

    Article  CAS  PubMed  Google Scholar 

  87. Hassan MI, Kumar V, Kashav T et al (2007) Proteomic approach for purification of seminal plasma proteins involved in tumor proliferation. J Sep Sci 30:1979–1988

    Article  CAS  PubMed  Google Scholar 

  88. WHO (2010) Laboratory manual for the examination and processing of human semen, 5th edn. WHO, Geneva

    Google Scholar 

  89. da Silva BF, Souza GH, lo Turco EG et al (2013) Differential seminal plasma proteome according to semen retrieval in men with spinal cord injury. Fertil Steril 100:959–969

    Article  PubMed  Google Scholar 

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  1. Biotechnology Division, Biomedical Research Foundation, Academy of Athens, Athens, 11527, Greece

    Vasiliki Lygirou, Manousos Makridakis & Antonia Vlahou Ph.D.

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  1. Vasiliki Lygirou
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  2. Manousos Makridakis
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  3. Antonia Vlahou Ph.D.
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Correspondence to Antonia Vlahou Ph.D. .

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  1. Biomedical Research Foundation, Academy of Athens, Athens, Greece

    Antonia Vlahou

  2. Biomedical Research Foundation, Academy of Athens, Athens, Greece

    Manousos Makridakis

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Lygirou, V., Makridakis, M., Vlahou, A. (2015). Biological Sample Collection for Clinical Proteomics: Existing SOPs. In: Vlahou, A., Makridakis, M. (eds) Clinical Proteomics. Methods in Molecular Biology, vol 1243. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1872-0_1

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