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AAPS PharmSciTech

, 20:146 | Cite as

Thermally Induced Denaturing Energetics of Human Blood Plasma Albumin by Differential Scanning Calorimetry (DSC) as an Indicator for Breast Cancer Diagnosis in Female Patients

  • Damrongsak FaroongsarngEmail author
  • Somkiat Sunpaweravong
  • Achara Raksawong
Research Article
  • 80 Downloads

Abstract

Cancerous invasion yields unusual metabolisms providing a significant amount of peptide albuminomes that modulate albumin stability via binding. The study aimed at the investigation of the thermal stability of human plasma albumin with breast cancer of various stages by means of differential scanning calorimetry (DSC). Blood plasma was drawn from 11 female breast cancer patients and 50 healthy volunteers of homogeneous demographics. Plasma samples and their albumin-enriched fractions were subjected to DSC scanning between 37 and 90°C at 5°C/min rate. For normal blood plasma, a characteristic signature of DSC tracing was observed. And, the deconvolution of DSC thermograms revealed the recognition of thermal transition of albumin. It was found that denaturing temperature of albumin increased with increasing breast cancer staging which implied the increase in albuminome/peptide abundance produced by cancerous invasion. The analysis of albumin denaturing energetics based on rational approximation of the simple Lumry-Eyring model demonstrated that thermal transition of free albumin and albuminome-bound form attained energetic levels expressed as apparent activation energy (Eapp ± s.e.) of 132.68 ± 14.21 and 46.76 ± 8.42 Kcal/mol corresponded to the schemes dominated by irreversible alteration and by reversible unfolding, respectively. Thus, Eapp value may indicate the degrees of cancerous invasion. It was proposed that Eapp may be used as an indicator to diagnose and assess the prognosis of breast cancer.

KEY WORDS

differential scanning calorimetry breast cancer Lumry-Eyring model human albumin albuminome 

Notes

Acknowledgements

Special thanks go to PSU Scientific Equipment Center, and Drug Delivery System Excellent Center, Faculty of Pharmaceutical Sciences for Lab facilities.

Funding Information

The authors are grateful to the Royal Golden Jubilee Ph. D. program for partial financial support and Thailand Research Fund as well as Prince of Songkla University for the co-funding research grant.

References

  1. 1.
    Virani S, Bilheem S, Chansaard W, Chitapanarux I, Daoprasert K, Khuanchana S, et al. National and subnational population-based incidence of cancer in Thailand: assessing cancers with the highest burdens. Cancers. 2017;9.  https://doi.org/10.3390/cancers9080108.CrossRefGoogle Scholar
  2. 2.
    Anderson NL, Anderson NG. The human plasma proteome: history, character, and diagnostic prospects. Mol Cell Proteomics. 2002;1:845–67.CrossRefGoogle Scholar
  3. 3.
    Koblinski JE, Ahram M, Sloane BF. Unraveling the role of proteases in cancer. Clin Chim Acta. 2000;291(2):113–35.CrossRefGoogle Scholar
  4. 4.
    Petricoin EF, Belluco C, Araujo RP, Liotta LA. The blood peptidome: a higher dimension of information content for cancer biomarker discovery. Nat Rev Cancer. 2006;6(12):961–7.CrossRefGoogle Scholar
  5. 5.
    Garbett NC, Miller JJ, Jenson AB, Chaires JB. Calorimetric analysis of the plasma proteome. Semin Nephrol. 2007;27(6):621–6.CrossRefGoogle Scholar
  6. 6.
    Garbett NC, Mekmaysy CS, Helm CW, Jenson AB, Chaires JB. Differential scanning calorimetry of blood plasma for clinical diagnosis and monitoring. Exp Mol Pathol. 2009;86:186–91.CrossRefGoogle Scholar
  7. 7.
    Garbett NC, Miller JJ, Jenson AB, Chaires JB. Calorimetry outside the box: a new window into the plasma proteome. Biophys J. 2008;94:1377–83.CrossRefGoogle Scholar
  8. 8.
    Vega S, Garcia-Gonzalez MA, Lanas A, Velazquez-Campoy A, Abian O. Deconvolution analysis for classifying gastric adenocarcinoma patients based on differential scanning calorimetry serum thermogram. Sci Rep. 2015;5:7988.CrossRefGoogle Scholar
  9. 9.
    Kikalishvili L, Ramishvili M, Nemsadze G, Lezhava T, Khorava P, Gorgoshidze M, et al. Thermal stability of blood plasma proteins of breast cancer patients, DSC study. J Therm Anal Calorim. 2015;120:501–5.CrossRefGoogle Scholar
  10. 10.
    Todinova S, Krumova S, Kurtev P, Dimitrov V, Djongov L, Dudunkov Z, et al. Calorimetry-based profiling of blood plasma from colorectal cancer patients. Biochim Biophys Acta. 2012;1820:1879–85.CrossRefGoogle Scholar
  11. 11.
    Zapf I, Fekecs T, Ferencz A, Tizedes G, Pavlovics G, Kalman E, et al. DSC analysis of human plasma in breast cancer patients. Thermochim Acta. 2011;524:88–91.CrossRefGoogle Scholar
  12. 12.
    Fasano M, Curry S, Terreno E, Galliano M, Fanali G, Narciso P, et al. The extraordinary ligand binding properties of human serum albumin. IUBMB Life. 2005;57(12):787–96.CrossRefGoogle Scholar
  13. 13.
    Gay M, Carrascal M, Gorga M, Pares A, Abian J. Characterization of peptides and proteins in commercial HSA solutions. Proteomics. 2010;10(2):172–81.CrossRefGoogle Scholar
  14. 14.
    Liu Z, Li S, Wang H, Tang M, Zhou M, Yu J, et al. Proteomic and network analysis of human serum albuminome by integrated use of quick crosslinking and two-step precipitation. Sci Rep. 2017;7:9856.CrossRefGoogle Scholar
  15. 15.
    Scumaci D, Gaspari M, Saccomanno M, Argiro G, Quaresima B, Faniello CM, et al. Assessment of an ad hoc procedure for isolation and characterization of human albuminome. Anal Biochem. 2011;418(1):161–3.CrossRefGoogle Scholar
  16. 16.
    Pico GA. Thermodynamic feature of the thermal unfolding of human serum albumin. Int J Biol Macromol. 1997;20:63–73.CrossRefGoogle Scholar
  17. 17.
    Sanchez-Ruiz JM. Theoretical analysis of Lumry-Eyring models in differential scanning calorimetry. Biophys J. 1992;61:921–35.CrossRefGoogle Scholar
  18. 18.
    Khrapunov S, Brenowitz M. Stability, denaturation and refolding of Mycobacvterium tuberculosis MfpA, a DNA mimicking protein that confers antibody resistant. Biophys Chem. 2011;159:33–40.CrossRefGoogle Scholar
  19. 19.
    Faroongsdarng D, Kongprasertkit J. The role of caprylate ligand ion on the stabilization of human serum albumin. AAPS PharmSciTech. 2014;15(2):465–71.CrossRefGoogle Scholar
  20. 20.
    Faroongsarng D. Assessment of the dissociation energetics of some selected ligand drugs bound on human serum albumin by differential scanning calorimetry. AAPS PharmSciTech. 2016;17(2):474–81.CrossRefGoogle Scholar
  21. 21.
    Singh KS, Kishore N. Thermodynamic insights into the binding of Triton X-100 to globular proteins: a calorimetric and spectroscopic investigation. J Phys Chem B. 2006;110(19):9728–37.CrossRefGoogle Scholar
  22. 22.
    Gress DM, Edge SB, Greene FL, Washington MK, Asare EA, Brierley JD, et al. Principle of cancer staging. In: Amin MB, et al., editors. : AJCC Cancer Staging Manual. American College of Surgeons; 2017.  https://doi.org/10.1007/978-3-319-40618-3_1.Google Scholar
  23. 23.
    Gundry RL, Fu Q, Jelinek CA, Van Eyk JE, Cotter RJ. Investigation of an albumin-enriched fraction of human serum and its albuminome. Proteomics Clin Appl. 2007;1:73–88.CrossRefGoogle Scholar
  24. 24.
    Arnold M, Leitzmann M, Freisling H, Bray F, Romieu I, Renehan A, et al. Obesity and cancer: an update of the global impact. Cancer Epidemiol. 2016;41:8–15.CrossRefGoogle Scholar
  25. 25.
    Chan DS, Vieira AR, Aune D, Bandera EV, Greenwood DC, McTiernan A, et al. Body mass index and survival in women with breast cancer-systematic literature review and meta-analysis of 82 follow-up studies. AnnOncol/ESMO. 2014;25(10):1901–14.Google Scholar
  26. 26.
    Koynova R, Antonova B, Sezanova B, Tenchov B. Beneficial effect of sequential chemotherapy treatments of lung cancer patients revealed by calorimetric monitoring of blood plasma proteome denaturation. Thermochim Acta. 2018;659:1–7.CrossRefGoogle Scholar
  27. 27.
    Kędra-Królik K, Chmielewska I, Michnik A, Zarzycki P. Blood serum calorimetry indicates the chemotherapeutic efficacy in lung cancer treatment. Sci Rep. 2017;7:16796.CrossRefGoogle Scholar
  28. 28.
    Farruggia B, Picó GA. Thermodynamic features of the chemical and thermal denaturations of human serum albumin. Int J Biol Macromol. 1999;26(5):317–23.CrossRefGoogle Scholar
  29. 29.
    Kim NA, Jin JH, Kim K-H, Lim DG, Cheong H, Kim YH, et al. Investigation of early and advanced stages in ovarian cancer using human plasma by differential scanning calorimetry and mass spectrometry. Arch Pharm Res. 2016;39:668–76.CrossRefGoogle Scholar
  30. 30.
    Sanchez-Ruiz JM. Ligand effects on protein thermodynamic stability. Biophys Chem. 2007;126:43–9.CrossRefGoogle Scholar
  31. 31.
    Fanali G, di Masi A, Trezza V, Marino M, Fasano M, Ascenzi P. Human serum albumin: from bench to bedside. Mol Asp Med. 2012;33:209–90.CrossRefGoogle Scholar
  32. 32.
    Shen Y, Tolic N, Liu T, Zhao R, Petritis BO, Gritsenko MA, et al. Blood peptidome-degradome profile of breast cancer. PLoS One. 2010;5(10):e13133.CrossRefGoogle Scholar
  33. 33.
    Garbett NC, Miller JJ, Jenson AB, Chaires JB. Ligand binding alters the calorimetric thermogram of albumin. J Clin Ligand Assay. 2007;29(4):194–7.Google Scholar
  34. 34.
    Celej MS, Dassie SA, Gonzalez M, Bianconi ML, Fidelio GD. Differential scanning calorimetry as a tool to estimate binding parameters in multiligand binding proteins. Anal Biochem. 2006;350:277–84.CrossRefGoogle Scholar
  35. 35.
    Arakawa T, Kita Y. Stabilizing effects of caprylate and acetyltryptophanate on heat-induced aggregation of bovine serum albumin. Biochim Biophys Acta. 2000;1479:32–6.CrossRefGoogle Scholar
  36. 36.
    Ascenzi P, Fasano M. Allostery in a monomeric protein: the case of human serum albumin. Biophys Chem. 2010;148(1–3):16–22.CrossRefGoogle Scholar
  37. 37.
    Sugio S, Kashima A, Mochizuki S, Noda M, Kobayashi K. Crystal structure of human serum albumin at 2.5 Å resolution. Protein Eng. 1999;12:439–46.CrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Damrongsak Faroongsarng
    • 1
    Email author
  • Somkiat Sunpaweravong
    • 2
  • Achara Raksawong
    • 1
  1. 1.Drug Delivery System Excellent Center, Department of Pharmaceutical Technology, Faculty of Pharmaceutical SciencePrince of Songkla UniversityHat YaiThailand
  2. 2.Department of Surgery, Faculty of MedicinePrince of Songkla UniversityHat YaiThailand

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