DOI QR코드

DOI QR Code

Elevated Serum Haptoglobin is Associated with Clinical Outcome in Triple-Negative Breast Cancer Patients

  • Tabassum, Umaira ;
  • Reddy, Obula ;
  • Mukherjee, Geetashree
  • Published : 2012.09.30

Abstract

Background: Breast cancer is the most common malignancy with the highest incidence rates among women worldwide. Triple-negative breast cancer (TNBC) disease is diagnosed more frequently in younger women, and is associated with a poor prognosis. Elevated levels of serum haptoglobin protein (Hp) are observed in many malignant diseases including breast cancer. We evaluated the expression and prognostic value of Hp among patients with TNBC. Materials and Methods: Serum Hp levels were determined by Elisa in 41 patients with TNBC and 10 normal individuals. Hp status was correlated with other clinico-pathological parameters including patient survival. Results: Of the 41 patients with TNBC, Hp over expression was detected in 24 (59%) by Elisa. Hp up-regulation was confirmed by Elisa based quantification in the serum of 41 TNBC patients against lower grades and 10 normal individuals. Survival analysis revealed that Hp ($p=2.016{\times}10^{-5}$), stage ($p=2.166{\times}10^{-5}$), distant metastasis ($p=2.217{\times}10^{-5}$), tumor size ($p=1.053{\times}10^{-5}$), and tumor grade (p=0.001), correlated with patient survival on univariate analysis. Multivariate analysis revealed that Hp (p=0.001), and grade of the disease (p=0.008) were independent predictors of survival. Conclusion: Our results indicate that serum levels of Hp may play a role as a potential serum biomarker and prognostic indicator among TNBC patients. Thus, Hp may present a new promising prognostic biomarker in TNBC patients, but independent validations are now necessary for confirmation.

Keywords

Triple negative breast cancer;Hp;prognosis;TNBC

References

  1. An JY, Fan ZM, Zhuang ZH, et al (2004). Proteomic analysis of blood level of proteins before and after operation in patients with esophageal squamous cell carcinoma at high-incidence area in Henan Province. World J Gastroenterol, 10, 3365-8.
  2. Awadallah SM, Atoum MF (2004). Haptoglobin polymorphism in breast cancer patients form Jordan. Clin Chim Acta, 341, 17-21. https://doi.org/10.1016/j.cccn.2003.10.032
  3. Bartel U, Elling D, Geserick (1985). Distribution of haptoglobin phenotypes in gynecologic tumors. Zentralbl Gynakol, 107, 1492-5.
  4. Beckman G, Eklund A, Frohlander N, et al (1986). Haptoglobin groups and lung cancer. Hum Hered, 36, 258-60. https://doi.org/10.1159/000153638
  5. Benkmann HG, Hanssen HP, Ovenbeck R, et al (1987). Distribution of alpha-1-antitrypsin and haptoglobin phenotypes in bladder cancer patients. Hum Hered, 37, 290-3. https://doi.org/10.1159/000153720
  6. Carlsson MC, Cederfur C, Schaar V, et al (2011). Galectin-1-binding glycoforms of haptoglobin with altered intracellular trafficking, and increase in metastatic breast cancer patients. PLoS One, 6, e26560. https://doi.org/10.1371/journal.pone.0026560
  7. Curigliano G, Goldhirsch A (2011). The triple-negative subtype: new ideas for the poorest prognosis breast cancer. J Natl Cancer Inst Monogr, 43, 108-10.
  8. Dunzendorfer U, Jung K, Ohlenschlager G, et al (1980). Transferrin, C3 complement, haptoglobin, plasminogen and alpha 2-microglobulin in patients with urogenital tumors. Eur Urol, 6, 232-6.
  9. Epelbaum R, Shalitin C, Segal R, et al (1998). Haptoglobinrelated protein as a serum marker in malignant lymphoma. Pathol Oncol Res, 4, 271-6. https://doi.org/10.1007/BF02905217
  10. Fornier M, Fumoleau P (2012). The paradox of triple negative breast cancer: novel approaches to treatment. Breast J, 18, 41-51. https://doi.org/10.1111/j.1524-4741.2011.01175.x
  11. Gast MC, van Tinteren H, Bontenbal M, et al (2008). Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients. BMC Cancer, 8, 389.
  12. Gluz O, Liedtke C, Gottschalk N, et al (2009). Triple-negative breast cancer-current status and future directions. Ann Oncol, 20, 1913-27. https://doi.org/10.1093/annonc/mdp492
  13. Kaur H, Bhardwaj DN, Shrivastava PK, et al (1984). Serum protein polymorphisms in breast cancer. Acta Anthropogenet, 8, 189-97.
  14. Kawai T (1995). Past, present and future of enzyme immunoassay. Nihon Rinsho, 53, 2101-6.
  15. Keam B, Im SA, Lee KH, et al (2011). Ki-67 can be used for further classification of triple negative breast cancer into two subtypes with different response and prognosis. Breast Cancer Res, 13, R22. https://doi.org/10.1186/bcr2834
  16. Kumar DM, Thota B, Shinde SV, et al (2010). Proteomic identification of haptoglobin alpha2 as a glioblastoma serum biomarker: implications in cancer cell migration and tumor growth. J Proteome Res, 9, 5557-67. https://doi.org/10.1021/pr1001737
  17. Lee DS, Kim SH, Suh YJ, et al (2011). Clinical implication of p53 overexpression in breast cancer patients younger than 50 years with a triple-negative subtype who undergo a modified radical mastectomy. Jpn J Clin Oncol, 41, 854-66. https://doi.org/10.1093/jjco/hyr066
  18. Mitchell RJ, Carzino R, Janardhana V (1988). Associations between the two serum proteins haptoglobin and transferrin and leukaemia. Hum Hered, 38, 144-50. https://doi.org/10.1159/000153775
  19. Sadrzadeh SM, Bozorgmehr J (2004). Haptoglobin phenotypes in health and disorders. Am J Clin Pathol, 121, S97-104.
  20. Tsamantanis C, Delinassios JG, Kottaridis S, et al (1980). Haptoglobin types in breast carcinoma. Hum Hered, 30, 44-5. https://doi.org/10.1159/000153087
  21. Zhao C, Annamalai L, Guo C, et al (2007). Circulating haptoglobin is an independent prognostic factor in the sera of patients with epithelial ovarian cancer. Neoplasia, 9, 1-7. https://doi.org/10.1593/neo.06619

Cited by

  1. Analysis of the differences of serum protein mass spectrometry in patients with triple negative breast cancer and non-triple negative breast cancer vol.35, pp.10, 2014, https://doi.org/10.1007/s13277-014-2221-5
  2. Haptoglobin expression correlates with tumor differentiation and five-year overall survival rate in hepatocellular carcinoma vol.12, pp.2, 2017, https://doi.org/10.1371/journal.pone.0171269
  3. Three gold indicators for breast cancer prognosis: a case–control study with ROC analysis for novel ratios related to CBC with (ALP and LDH) pp.1573-4978, 2019, https://doi.org/10.1007/s11033-019-04650-9