Biotechnology and Bioprocess Engineering

, Volume 24, Issue 2, pp 343–358 | Cite as

Method Validation by CPTAC Guidelines for Multi-protein Marker Assays Using Multiple Reaction Monitoring-mass Spectrometry

  • Minsoo Son
  • Hyunsoo Kim
  • Injoon Yeo
  • Yoseop Kim
  • Areum Sohn
  • Youngsoo KimEmail author
Research Paper


Quantifying multiple protein biomarkers in a blood sample at one time has many advantages for diagnosing human diseases. In this study, 34 multiplex assays by multiple reaction monitoring-mass spectrometry (MRM-MS) for serum biomarkers were characterized according to Clinical Proteomic Tumor Analysis Consortium (CPTAC) guidelines. The assays revealed that the median lower limit of quantitation (LLOQ) was 0.37 fmol/μL (16.0 ng/mL) and that the median total coefficient of variation (CV) was 18.2%, 12.2%, and 10.6% in the low-,medium-, and high-quality control (QC) samples. With regard to selectivity, the median mean differences in slope and concentration were 2.1% and 4.3%, respectively. The median values for all CVs and %difference from the nominal concentration for stability were 9.5% and 2.7% in low-QC and 3.8% and 3.1% in medium-QC. The median total CV was 9.8% in the reproducibility. Finally, 17 protein-based biomarker assays were reliable and transferrable for preclinical purposes per CPTAC guidelines.


MRM-MS LC-MS/MS CPTAC guidelines method validation quantitative proteomics 


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Hyunsoo Kim and Youngsoo Kim contributed to study concept and design; Minsoo Son and Hyunsoo Kim contributed to acquisition of data; Injoon Yeo contributed to statistical analysis; Youngsoo Kim contributed to obtained funding; Yoseop Kim and Areum Sohn contributed to administrative, technical, or material support; Minsoo Son, Hyunsoo Kim and Youngsoo Kim contributed to drafting of the manuscript. #These authors contributed equally.

This work was supported by the Industrial Strategic Technology Development Program (#10079271 and #2000134) and the Collaborative Genome Program for Fostering New Post-Genome Industry (NRF-2017M3C9A5031597), funded from the Korean Government. This study was also supported by a grant from Seoul National University Hospital (2019).

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  1. 1.
    Whiteaker, J. R., C. Lin, J. Kennedy, L. Hou, M. Trute, I. Sokal, P. Yan, R. M. Schoenherr, L. Zhao, U. J. Voytovich, K. S. Kelly-Spratt, A. Krasnoselsky, P. R. Gafken, J. M. Hogan, L. A. Jones, P. Wang, L. Amon, L. A. Chodosh, P. S. Nelson, M. W. McIntosh, C. J. Kemp, and A. G. Paulovich (2011) A targeted proteomics-based pipeline for verification of biomarkers in plasma. Nature Biotechnology 29: 625–634.CrossRefGoogle Scholar
  2. 2.
    Chen, Y., Y. Zhang, Y. Yin, G. Gao, S. Li, Y. Jiang, X. Gu, and J. Luo (2005) SPD — a web-based secreted protein database. Nucleic Acids Res. 33: D169–173.CrossRefGoogle Scholar
  3. 3.
    Jackson, G. S., J. Burk-Rafel, J. A. Edgeworth, A. Sicilia, S. Abdilahi, J. Korteweg, J. Mackey, C. Thomas, G. Wang, J. M. Schott, C. Mummery, P. F. Chinnery, S. Mead, and J. Collinge (2014) Population screening for variant Creutzfeldt-Jakob disease using a novel blood test: diagnostic accuracy and feasibility study. JAMA Neurology 71: 421–428.CrossRefGoogle Scholar
  4. 4.
    Werner, S., F. Krause, V. Rolny, M. Strobl, D. Morgenstern, C. Datz, H. Chen, and H. Brenner (2016) Evaluation of a 5-marker blood test for colorectal cancer early detection in a colorectal cancer screening setting. Clinical Cancer Research: an Official Journal of the American Association for Cancer Research 22: 1725–1733.CrossRefGoogle Scholar
  5. 5.
    Anderson, N. L. (2010) The clinical plasma proteome: a survey of clinical assays for proteins in plasma and serum. Clinical Chemistry 56: 177–185.CrossRefGoogle Scholar
  6. 6.
    Duffy, M. J., A. van Dalen, C. Haglund, L. Hansson, E. Holinski-Feder, R. Klapdor, R. Lamerz, P. Peltomaki, C. Sturgeon, and O. Topolcan (2007) Tumour markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines for clinical use. European Journal of Cancer 43: 1348–1360.CrossRefGoogle Scholar
  7. 7.
    Hudler, P., N. Kocevar, and R. Komel (2014) Proteomic approaches in biomarker discovery: new perspectives in cancer diagnostics. TheScientificWorldJournal. 2014: 260348.CrossRefGoogle Scholar
  8. 8.
    Srivastava, S., M. Verma, and D. E. Henson (2001) Biomarkers for early detection of colon cancer. Clinical Cancer Research: an Official Journal of the American Association for Cancer Research 7: 1118–1126.Google Scholar
  9. 9.
    Kim, H., S. J. Yu, I. Yeo, Y. Y. Cho, D. H. Lee, Y. Cho, E. J. Cho, J. H. Lee, Y. J. Kim, S. Lee, J. Jun, T. Park, J. H. Yoon, and Y. Kim (2017) Prediction of response to sorafenib in hepatocellular carcinoma: a putative marker panel by multiple reaction monitoring-mass spectrometry (MRM-MS). Molecular & Cellular Proteomics: MCP 16: 1312–1323.CrossRefGoogle Scholar
  10. 10.
    Yu, S. J., H. Kim, H. Min, A. Sohn, Y. Y. Cho, J. J. Yoo, D. H. Lee, E. J. Cho, J. H. Lee, J. Gim, T. Park, Y. J. Kim, C. Y. Kim, J. H. Yoon, and Y. Kim (2017) Targeted proteomics predicts a sustained complete-response after transarterial chemoembolization and clinical outcomes in patients with hepatocellular carcinoma: a prospective cohort study. Journal of Proteome Research 16: 1239–1248.CrossRefGoogle Scholar
  11. 11.
    Yurkovetsky, Z., S. Skates, A. Lomakin, B. Nolen, T. Pulsipher, F. Modugno, J. Marks, A. Godwin, E. Gorelik, I. Jacobs, U. Menon, K. Lu, D. Badgwell, R. C. Bast, Jr., and A. E. Lokshin (2010) Development of a multimarker assay for early detection of ovarian cancer. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 28: 2159–2166.CrossRefGoogle Scholar
  12. 12.
    Brennan, D. J., D. P. O’Connor, E. Rexhepaj, F. Ponten, and W. M. Gallagher (2010) Antibody-based proteomics: fast-tracking molecular diagnostics in oncology. Nature Reviews Cancer 10: 605–617.CrossRefGoogle Scholar
  13. 13.
    Stahl-Zeng, J., V. Lange, R. Ossola, K. Eckhardt, W. Krek, R. Aebersold, and B. Domon (2007) High sensitivity detection of plasma proteins by multiple reaction monitoring of N-glycosites. Molecular & Cellular Proteomics: MCP 6: 1809–1817.CrossRefGoogle Scholar
  14. 14.
    Li, H., S. Bergeron, and D. Juncker (2012) Microarray-to-microarray transfer of reagents by snapping of two chips for cross-reactivity-free multiplex immunoassays. Analytical Chemistry 84: 4776–4783.CrossRefGoogle Scholar
  15. 15.
    Pla-Roca, M., R. F. Leulmi, S. Tourekhanova, S. Bergeron, V. Laforte, E. Moreau, S. J. Gosline, N. Bertos, M. Hallett, M. Park, and D. Juncker (2012) Antibody colocalization microarray: a scalable technology for multiplex protein analysis in complex samples. Molecular & Cellular Proteomics: MCP 11: M111 011460.CrossRefGoogle Scholar
  16. 16.
    Kennedy, J. J., S. E. Abbatiello, K. Kim, P. Yan, J. R. Whiteaker, C. Lin, J. S. Kim, Y. Zhang, X. Wang, R. G. Ivey, L. Zhao, H. Min, Y. Lee, M. H. Yu, E. G. Yang, C. Lee, P. Wang, H. Rodriguez, Y. Kim, S. A. Carr, and A. G. Paulovich (2014) Demonstrating the feasibility of large-scale development of standardized assays to quantify human proteins. Nature Methods 11: 149–155.CrossRefGoogle Scholar
  17. 17.
    Picotti, P. and R. Aebersold (2012) Selected reaction monitoring-based proteomics: workflows, potential, pitfalls and future directions. Nature Methods 9: 555–566.CrossRefGoogle Scholar
  18. 18.
    Gillette, M. A. and S. A. Carr (2013) Quantitative analysis of peptides and proteins in biomedicine by targeted mass spectrometry. Nature Methods 10: 28–34.CrossRefGoogle Scholar
  19. 19.
    Yang, T., F. Chen, F. Xu, F. Wang, Q. Xu, and Y. Chen (2014) A liquid chromatography-tandem mass spectrometry-based targeted proteomics assay for monitoring P-glycoprotein levels in human breast tissue. Clinica Chimica Acta; International Journal of Clinical Chemistry 436: 283–289.CrossRefGoogle Scholar
  20. 20.
    Abbatiello, S. E., D. R. Mani, B. Schilling, B. Maclean, L. J. Zimmerman, X. Feng, M. P. Cusack, N. Sedransk, S. C. Hall, T. Addona, S. Allen, N. G. Dodder, M. Ghosh, J. M. Held, V. Hedrick, H. D. Inerowicz, A. Jackson, H. Keshishian, J. W. Kim, J. S. Lyssand, C. P. Riley, P. Rudnick, P. Sadowski, K. Shaddox, D. Smith, D. Tomazela, A. Wahlander, S. Waldemarson, C. A. Whitwell, J. You, S. Zhang, C. R. Kinsinger, M. Mesri, H. Rodriguez, C. H. Borchers, C. Buck, S. J. Fisher, B. W. Gibson, D. Liebler, M. Maccoss, T. A. Neubert, A. Paulovich, F. Regnier, S. J. Skates, P. Tempst, M. Wang, and S. A. Carr (2013) Design, implementation and multisite evaluation of a system suitability protocol for the quantitative assessment of instrument performance in liquid chromatography-multiple reaction monitoring-MS (LC-MRM-MS). Molecular & Cellular Proteomics: MCP 12: 2623–2639.CrossRefGoogle Scholar
  21. 21.
    Abbatiello, S. E., B. Schilling, D. R. Mani, L. J. Zimmerman, S. C. Hall, B. MacLean, M. Albertolle, S. Allen, M. Burgess, M. P. Cusack, M. Gosh, V. Hedrick, J. M. Held, H. D. Inerowicz, A. Jackson, H. Keshishian, C. R. Kinsinger, J. Lyssand, L. Makowski, M. Mesri, H. Rodriguez, P. Rudnick, P. Sadowski, N. Sedransk, K. Shaddox, S. J. Skates, E. Kuhn, D. Smith, J. R. Whiteaker, C. Whitwell, S. Zhang, C. H. Borchers, S. J. Fisher, B. W. Gibson, D. C. Liebler, M. J. MacCoss, T. A. Neubert, A. G. Paulovich, F. E. Regnier, P. Tempst, and S. A. Carr (2015) Large-scale interlaboratory study to develop, analytically validate and apply highly multiplexed, quantitative peptide assays to measure cancer-relevant proteins in plasma. Molecular & Cellular Proteomics: MCP 14: 2357–2374.CrossRefGoogle Scholar
  22. 22.
    Addona, T. A., S. E. Abbatiello, B. Schilling, S. J. Skates, D. R. Mani, D. M. Bunk, C. H. Spiegelman, L. J. Zimmerman, A. J. Ham, H. Keshishian, S. C. Hall, S. Allen, R. K. Blackman, C. H. Borchers, C. Buck, H. L. Cardasis, M. P. Cusack, N. G. Dodder, B. W. Gibson, J. M. Held, T. Hiltke, A. Jackson, E. B. Johansen, C. R. Kinsinger, J. Li, M. Mesri, T. A. Neubert, R. K. Niles, T. C. Pulsipher, D. Ransohoff, H. Rodriguez, P. A. Rudnick, D. Smith, D. L. Tabb, T. J. Tegeler, A. M. Variyath, L. J. Vega-Montoto, A. Wahlander, S. Waldemarson, M. Wang, J. R. Whiteaker, L. Zhao, N. L. Anderson, S. J. Fisher, D. C. Liebler, A. G. Paulovich, F. E. Regnier, P. Tempst, and S. A. Carr (2009) Multi-site assessment of the precision and reproducibility of multiple reaction monitoring-based measurements of proteins in plasma. Nature Biotechnology 27: 633–641.CrossRefGoogle Scholar
  23. 23.
    Carr, S. A., S. E. Abbatiello, B. L. Ackermann, C. Borchers, B. Domon, E. W. Deutsch, R. P. Grant, A. N. Hoofnagle, R. Huttenhain, J. M. Koomen, D. C. Liebler, T. Liu, B. MacLean, D. R. Mani, E. Mansfield, H. Neubert, A. G. Paulovich, L. Reiter, O. Vitek, R. Aebersold, L. Anderson, R. Bethem, J. Blonder, E. Boja, J. Botelho, M. Boyne, R. A. Bradshaw, A. L. Burlingame, D. Chan, H. Keshishian, E. Kuhn, C. Kinsinger, J. S. Lee, S. W. Lee, R. Moritz, J. Oses-Prieto, N. Rifai, J. Ritchie, H. Rodriguez, P. R. Srinivas, R. R. Townsend, J. Van Eyk, G. Whiteley, A. Wiita, and S. Weintraub (2014) Targeted peptide measurements in biology and medicine: best practices for mass spectrometry-based assay development using a fit-for-purpose approach. Molecular & Cellular Proteomics: MCP 13: 907–917.CrossRefGoogle Scholar
  24. 24.
    Whiteaker, J. R., G. N. Halusa, A. N. Hoofnagle, V. Sharma, B. MacLean, P. Yan, J. A. Wrobel, J. Kennedy, D. R. Mani, L. J. Zimmerman, M. R. Meyer, M. Mesri, H. Rodriguez, C. Clinical Proteomic Tumor Analysis, and A. G. Paulovich (2014) CPTAC Assay Portal: a repository of targeted proteomic assays. Nature Methods 11: 703–704.CrossRefGoogle Scholar
  25. 25.
    MacLean, B., D. M. Tomazela, N. Shulman, M. Chambers, G. L. Finney, B. Frewen, R. Kern, D. L. Tabb, D. C. Liebler, and M. J. MacCoss (2010) Skyline: an open source document editor for creating and analyzing targeted proteomics experiments. Bioinformatics 26: 966–968.CrossRefGoogle Scholar
  26. 26.
    Abbatiello, S. E., D. R. Mani, H. Keshishian, and S. A. Carr (2010) Automated detection of inaccurate and imprecise transitions in peptide quantification by multiple reaction monitoring mass spectrometry. Clinical Chemistry 56: 291–305.CrossRefGoogle Scholar
  27. 27.
    Hortin, G. L., D. Sviridov, and N. L. Anderson (2008) High-abundance polypeptides of the human plasma proteome comprising the top 4 logs of polypeptide abundance. Clinical Chemistry 54: 1608–1616.CrossRefGoogle Scholar
  28. 28.
    Kim, K., J. Yu, H. Min, H. Kim, B. Kim, H. G. Yu, and Y. Kim (2010) Online monitoring of immunoaffinity-based depletion of high-abundance blood proteins by UV spectrophotometry using enhanced green fluorescence protein and FITC-labeled human serum albumin. Proteome Science 8: 62.CrossRefGoogle Scholar
  29. 29.
    Stein, S. E. and D. R. Scott (1994) Optimization and testing of mass spectral library search algorithms for compound identification. Journal of the American Society for Mass Spectrometry 5: 859–866.CrossRefGoogle Scholar
  30. 30.
    Altschul, S. F., W. Gish, W. Miller, E. W. Myers, and D. J. Lipman (1990) Basic local alignment search tool. Journal of Molecular Biology 215: 403–410.CrossRefGoogle Scholar
  31. 31.
    FDA (2013) Guidance for Industry Bioanalytical Method Validation. In: Editor (ed.) (eds.). Book Title. Publisher, City.Google Scholar
  32. 32.
    C62-A. (2014) Liquid Chromatography-Mass Spectrometry Methods; Approved Guideline. Clinical and Laboratory and Standards Institute (CLSI), Wayne, PA.Google Scholar
  33. 33.
    Unsworth, D. J. (2008) Complement deficiency and disease. Journal of Clinical Pathology 61: 1013–1017.CrossRefGoogle Scholar
  34. 34.
    Walport, M. J. (2001) Complement. First of two parts. The New England Journal of Medicine 344: 1058–1066.CrossRefGoogle Scholar
  35. 35.
    Walport, M. J. (2001) Complement. Second of two parts. The New England Journal of Medicine 344: 1140–1144.CrossRefGoogle Scholar
  36. 36.
    Yavuz, S. and T. O. Acarturk (2010) Acquired partial lipodystrophy with C3 hypocomplementemia and antiphospholipid and anticardiolipin antibodies. Pediatric Dermatology 27: 504–508.CrossRefGoogle Scholar
  37. 37.
    Inai, S., Y. Akagaki, T. Moriyama, Y. Fukumori, K. Yoshimura, S. Ohnoki, and H. Yamaguchi (1989) Inherited deficiencies of the late-acting complement components other than C9 found among healthy blood donors. International Archives of Allergy and Applied Immunology 90: 274–279.CrossRefGoogle Scholar
  38. 38.
    Pereira de Carvalho Florido, M., P. Ferreira de Paula, and L. Isaac (2003) Simple method to distinguish between primary and secondary C3 deficiencies. Clinical and Diagnostic Laboratory Immunology 10: 216–220.Google Scholar
  39. 39.
    Thurman, J. M. (2015) Complement in kidney disease: core curriculum 2015. American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation 65: 156–168.CrossRefGoogle Scholar
  40. 40.
    Zuraw, B. L. (2008) Clinical practice. Hereditary angioedema. The New England Journal of Medicine 359: 1027–1036.CrossRefGoogle Scholar
  41. 41.
    Asakai, R., D. W. Chung, O. D. Ratnoff, and E. W. Davie (1989) Factor XI (plasma thromboplastin antecedent) deficiency in Ashkenazi Jews is a bleeding disorder that can result from three types of point mutations. Proceedings of the National Academy of Sciences of the United States of America 86: 7667–7671.CrossRefGoogle Scholar
  42. 42.
    Carpenter, S. L., and P. Mathew (2008) Alpha2-antiplasmin and its deficiency: fibrinolysis out of balance. Haemophilia: the official journal of the World Federation of Hemophilia 14: 1250–1254.CrossRefGoogle Scholar
  43. 43.
    Gupta, P. K., H. Kumar, and S. Kumar (2008) Hereditary Factor X (Stuart-Prower Factor) Deficiency. Medical Journal, Armed Forces India 64: 286–287.CrossRefGoogle Scholar
  44. 44.
    Margaglione, M. and E. Grandone (2011) Population genetics of venous thromboembolism. A narrative review. Thrombosis and Haemostasis 105: 221–231.CrossRefGoogle Scholar
  45. 45.
    Mehta, R. and A. D. Shapiro (2008) Plasminogen deficiency. Haemophilia: the Official Journal of the World Federation of Hemophilia 14: 1261–1268.CrossRefGoogle Scholar
  46. 46.
    Montgomery, R. R., A. Otsuka, and W. E. Hathaway (1978) Hypoprothrombinemia: case report. Blood 51: 299–306.Google Scholar
  47. 47.
    Yousuf, O., B. D. Mohanty, S. S. Martin, P. H. Joshi, M. J. Blaha, K. Nasir, R. S. Blumenthal, and M. J. Budoff (2013) High-sensitivity C-reactive protein and cardiovascular disease: a resolute belief or an elusive link? Journal of the American College of Cardiology 62: 397–408.CrossRefGoogle Scholar
  48. 48.
    Gabay, C. and I. Kushner (1999) Acute-phase proteins and other systemic responses to inflammation. The New England Journal of Medicine 340: 448–454.CrossRefGoogle Scholar
  49. 49.
    Macy, E. M., T. E. Hayes, and R. P. Tracy (1997) Variability in the measurement of C-reactive protein in healthy subjects: implications for reference intervals and epidemiological applications. Clinical Chemistry 43: 52–58.Google Scholar
  50. 50.
    Walldius, G., and I. Jungner (2006) The apoB/apoA-I ratio: a strong, new risk factor for cardiovascular disease and a target for lipid-lowering therapy— a review of the evidence. Journal of Internal Medicine 259: 493–519.CrossRefGoogle Scholar
  51. 51.
    Ding, E. L., Y. Song, J. E. Manson, D. J. Hunter, C. C. Lee, N. Rifai, J. E. Buring, J. M. Gaziano, and S. Liu (2009) Sex hormone-binding globulin and risk of type 2 diabetes in women and men. The New England Journal of Medicine 361: 1152–1163.CrossRefGoogle Scholar
  52. 52.
    Ley, S. H., S. B. Harris, P. W. Connelly, M. Mamakeesick, J. Gittelsohn, T. M. Wolever, R. A. Hegele, B. Zinman, and A. J. Hanley (2010) Association of apolipoprotein B with incident type 2 diabetes in an aboriginal Canadian population. Clinical Chemistry 56: 666–670.CrossRefGoogle Scholar
  53. 53.
    Ruokonen, A., M. Alen, N. Bolton, and R. Vihko (1985) Response of serum testosterone and its precursor steroids, SHBG and CBG to anabolic steroid and testosterone self-administration in man. Journal of Steroid Biochemistry 23: 33–38.CrossRefGoogle Scholar
  54. 54.
    Acchiardo, S., A. P. Kraus, Jr., and B. R. Jennings (1989) Beta 2-microglobulin levels in patients with renal insufficiency. American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation 13: 70–74.CrossRefGoogle Scholar
  55. 55.
    Hojs, R., S. Bevc, R. Ekart, M. Gorenjak, and L. Puklavec (2006) Serum cystatin C as an endogenous marker of renal function in patients with mild to moderate impairment of kidney function. Nephrology, Dialysis, Transplantation: Official Publication of the European Dialysis and Transplant Association—European Renal Association 21: 1855–1862.CrossRefGoogle Scholar
  56. 56.
    Keevil, B. G., E. S. Kilpatrick, S. P. Nichols, and P. W. Maylor (1998) Biological variation of cystatin C: implications for the assessment of glomerular filtration rate. Clinical Chemistry 44: 1535–1539.Google Scholar
  57. 57.
    deWilde, A., K. Sadilkova, M. Sadilek, V. Vasta, and S. H. Hahn (2008) Tryptic peptide analysis of ceruloplasmin in dried blood spots using liquid chromatography-tandem mass spectrometry: application to newborn screening. Clinical Chemistry 54: 1961–1968.CrossRefGoogle Scholar
  58. 58.
    Garewal, H., B. G. Durie, R. A. Kyle, P. Finley, B. Bower, and R. Serokman (1984) Serum beta 2-microglobulin in the initial staging and subsequent monitoring of monoclonal plasma cell disorders. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 2: 51–57.CrossRefGoogle Scholar
  59. 59.
    Li, X. and J. N. Buxbaum (2011) Transthyretin and the brain revisited: is neuronal synthesis of transthyretin protective in Alzheimer’s disease? Molecular Neurodegeneration 6: 79.CrossRefGoogle Scholar
  60. 60.
    Maiorana, A. and R. B. Roach, Jr. (2003) Heterozygous pseudocholinesterase deficiency: a case report and review of the literature. Journal of Oral and Maxillofacial Surgery: Official Journal of the American Association of Oral and Maxillofacial Surgeons 61: 845–847.CrossRefGoogle Scholar
  61. 61.
    Rodriguez, J., J. Cortes, M. Talpaz, S. O’Brien, T. L. Smith, M. B. Rios, and H. Kantarjian (2000) Serum beta-2 microglobulin levels are a significant prognostic factor in Philadelphia chromosome-positive chronic myelogenous leukemia. Clinical Cancer Research: an Official Journal of the American Association for Cancer Research 6: 147–152.Google Scholar
  62. 62.
    Shen, Y., J. Zhang, Y. Zhao, Y. Yan, Y. Liu, and J. Cai (2015) Diagnostic value of serum IGF-1 and IGFBP-3 in growth hormone deficiency: a systematic review with meta-analysis. European Journal of Pediatrics 174: 419–427.CrossRefGoogle Scholar
  63. 63.
    Westermark, P., K. Sletten, B. Johansson, and G. G. Cornwell, 3rd (1990) Fibril in senile systemic amyloidosis is derived from normal transthyretin. Proceedings of the National Academy of Sciences of the United States of America 87: 2843–2845.CrossRefGoogle Scholar
  64. 64.
    Logdberg, L. E., B. Akerstrom, and S. Badve (2000) Tissue distribution of the lipocalin alpha-1 microglobulin in the developing human fetus. The Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society 48: 1545–1552.CrossRefGoogle Scholar
  65. 65.
    Penders, J. and J. R. Delanghe (2004) Alpha 1-microglobulin: clinical laboratory aspects and applications. Clinica Chimica Acta; International Journal of Clinical Chemistry 346: 107–118.CrossRefGoogle Scholar
  66. 66.
    Keramat, L., H. Sadrzadeh-Yeganeh, G. Sotoudeh, E. Zamani, M. Eshraghian, A. Mansoori, and F. Koohdani (2017) Apolipoprotein A2 -265 T>C polymorphism interacts with dietary fatty acids intake to modulate inflammation in type 2 diabetes mellitus patients. Nutrition (Burbank, Los Angeles County, Calif.) 37: 86–91.CrossRefGoogle Scholar
  67. 67.
    Kobayashi, T., Y. Sato, S. Nishiumi, Y. Yagi, A. Sakai, H. Shiomi, A. Masuda, S. Okaya, H. Kutsumi, M. Yoshida, and K. Honda (2018) Serum apolipoprotein A2 isoforms in autoimmune 497: 903–907.Google Scholar
  68. 68.
    Marais, A. D. (2018) Apolipoprotein E in lipoprotein metabolism, health and cardiovascular disease. Pathology Google Scholar
  69. 69.
    Morris, J. C., S. E. Schindler, L. M. McCue, K. L. Moulder, T. L. S. Benzinger, C. Cruchaga, A. M. Fagan, E. Grant, B. A. Gordon, D. M. Holtzman, and C. Xiong (2019) Assessment of racial disparities in biomarkers for Alzheimer disease. JAMA Neurology Google Scholar
  70. 70.
    Kamboh, M. I., S. Manzi, H. Mehdi, S. Fitzgerald, D. K. Sanghera, L. H. Kuller, and C. E. Atson (1999) Genetic variation in apolipoprotein H (beta2-glycoprotein I) affects the occurrence of antiphospholipid antibodies and apolipoprotein H concentrations in systemic lupus erythematosus. Lupus 8: 742–750.CrossRefGoogle Scholar
  71. 71.
    Vogrinc, Z., M. Trbojevic-Cepe, D. Coen, K. Vitale, and A. Stavljenic-Rukavina (2005) Apolipoprotein H (apoH)-dependent autoantibodies and apoH protein polymorphism in selected patients showing lupus anticoagulant activity. Clinical Chemistry and Laboratory Medicine 43: 17–21.CrossRefGoogle Scholar
  72. 72.
    Horvath-Szalai, Z., P. Kustan, D. Muhl, A. Ludany, B. Bugyi, and T. Koszegi (2017) Antagonistic sepsis markers: Serum gelsolin and actin/gelsolin ratio. Clinical Biochemistry 50: 127–133.CrossRefGoogle Scholar
  73. 73.
    Huang, L. F., Y. M. Yao, J. F. Li, N. Dong, C. Liu, Y. Yu, L. X. He, and Z. Y. Sheng (2011) Reduction of plasma gelsolin levels correlates with development of multiple organ dysfunction syndrome and fatal outcome in burn patients. PLoS One 6: e25748.CrossRefGoogle Scholar
  74. 74.
    Wu, C., T. Shi, J. N. Brown, J. He, Y. Gao, T. L. Fillmore, A. K. Shukla, R. J. Moore, D. G. Camp, 2nd, K. D. Rodland, W. J. Qian, T. Liu, and R. D. Smith (2014) Expediting SRM assay development for large-scale targeted proteomics experiments. Journal of Proteome Research 13: 4479–4487.CrossRefGoogle Scholar
  75. 75.
    Percy, A. J., A. G. Chambers, J. Yang, D. Domanski, and C. H. Borchers (2012) Comparison of standard- and nano-flow liquid chromatography platforms for MRM-based quantitation of putative plasma biomarker proteins. Anal Bioanal Chem. 404: 1089–1101.CrossRefGoogle Scholar

Copyright information

© The Korean Society for Biotechnology and Bioengineering and Springer 2019

Authors and Affiliations

  • Minsoo Son
    • 1
  • Hyunsoo Kim
    • 1
    • 2
    • 3
  • Injoon Yeo
    • 1
  • Yoseop Kim
    • 1
  • Areum Sohn
    • 2
  • Youngsoo Kim
    • 1
    • 2
    • 3
    Email author
  1. 1.Departments of Biomedical EngineeringSeoul National University College of MedicineSeoulKorea
  2. 2.Departments of Biomedical SciencesSeoul National University College of MedicineSeoulKorea
  3. 3.Institute of Medical and Biological EngineeringMedical Research CenterSeoulKorea

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