Advertisement

Tumor Biology

, Volume 36, Issue 6, pp 4793–4799 | Cite as

Elevated expression of HABP1 is a novel prognostic indicator in triple-negative breast cancers

  • Ji Wang
  • Yanni Song
  • Tong Liu
  • Qingyu Shi
  • Zhenbin Zhong
  • Wei Wei
  • Suyun Huang
  • Da Pang
Research Article

Abstract

Hyaluronan-binding protein 1 (HABP1) has been documented to overexpress in several malignancies. The aim of our study is to investigate the expression of HABP1 protein in triple-negative breast cancer (TNBC) and its clinical significance. Using immunohistochemistry, HABP1 expression was evaluated in 139 TNBC specimens. The association between HABP1 expression with clinicopathological parameters was assessed using chi-square test. The survival status of patients was analyzed using the Kaplan–Meier and log-rank tests. Cox regression was used for the multivariate analysis of prognostic factors. The results showed that HABP1 overexpression correlated with higher histological grade (P = 0.004), advanced TNM stage (P = 0.008), greater tumor size (P = 0.016), metastasis of lymph node (P < 0.001), and recurrence (P = 0.040). Furthermore, it indicated that patients with HABP1 overexpression had significantly poorer overall survival (OS) and disease-free survival (DFS) compared with patients (P < 0.001 for both). Multivariate Cox regression analysis revealed that elevated HABP1 expression was an independent prognostic factor for both OS (P = 0.035) and DFS (P = 0.013). In contrast to the effect of HABP1 in TNBCs with lymph node metastasis, HABP1 overexpression significantly affects prognosis (OS, P = 0.002; DFS, P = 0.003) in TNBCs without lymph node metastasis. In conclusion, HABP1 protein high expression may contribute to the tumor progression and poor prognosis of TNBC, especially in predicting prognosis in TNBCs without lymph node metastasis.

Keywords

Hyaluronan-binding protein 1 Triple-negative breast cancer Prognosis Metastasis 

Notes

Conflicts of interest

None

References

  1. 1.
    Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V. Descriptive analysis of estrogen receptor (ER)-negative, PR-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer. 2007;109(9):1721–8.CrossRefPubMedGoogle Scholar
  2. 2.
    Kilburn LS. TNT Trial Management Group. ‘Triple negative’ breast cancer: a new area for phase III breast cancer clinical trials. Clin Oncol R Coll Radiol. 2008;20(1):35–9.CrossRefPubMedGoogle Scholar
  3. 3.
    Reis-Filho JS, Tutt AN. Triple negative tumors: a critical review. Histopathology. 2008;52(1):108–18.CrossRefPubMedGoogle Scholar
  4. 4.
    Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010;28(16):2784–95.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Lin NU, Vanderplas A, Hughes ME, Theriault RL, Edge SB, Wong YN, et al. Clinicopathologic features, patterns of recurrence, and survival among women with triple-negative breast cancer in the National Comprehensive Cancer Network. Cancer. 2012;118(22):5463–72.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13(15 Pt 1):4429–34.CrossRefPubMedGoogle Scholar
  7. 7.
    Gupta S, Datta K. Possible role of hyaluronectin on cell adhesion in rat histiocytoma. Exp Cell Res. 1991;195(2):386–94.CrossRefPubMedGoogle Scholar
  8. 8.
    Deb TB, Datta K. Molecular cloning of human fibroblast hyaluronic acid-binding protein confirms its identity with P-32, a protein co-purified with splicing factor SF2. Hyaluronic acid-binding protein as P-32 protein, co-purified with splicing factor SF2. J Biol Chem. 1996;271(4):2206–12.CrossRefPubMedGoogle Scholar
  9. 9.
    Majumdar M, Datta K. Assignment of cDNA encoding hyaluronic acid-binding protein 1 to human chromosome 17p12-p13. Genomics. 1998;51(3):476–7.CrossRefPubMedGoogle Scholar
  10. 10.
    Krainer AR, Mayeda A, Kozak D, Binns G. Functional expression of cloned human splicing factor SF2: homology to RNA-binding proteins, U1 70 K, and Drosophila splicing regulators. Cell. 1991;66(2):383–94.CrossRefPubMedGoogle Scholar
  11. 11.
    Ranganathan S, Ganguly AK, Datta K. Evidence for presence of hyaluronan binding protein on spermatozoa and its possible involvement in sperm function. Mol Reprod Dev. 1994;38(1):69–76.CrossRefPubMedGoogle Scholar
  12. 12.
    Das S, Deb TB, Kumar R, Datta K. Multifunctional activities of human fibroblast 34-kDa hyaluronic acid-binding protein. Gene. 1997;190(1):223–5.CrossRefPubMedGoogle Scholar
  13. 13.
    Rao CM, Deb TB, Datta K. Hyaluronic acid induced hyaluronic acid binding protein phosphorylation and inositol triphosphate formation in lymphocytes. Biochem Mol Biol Int. 1996;40(2):327–37.PubMedGoogle Scholar
  14. 14.
    Rao CM, Deb TB, Gupta S, Datta K. Regulation of cellular phosphorylation of hyaluronan binding protein and its role in the formation of second messenger. Biochim Biophys Acta. 1997;1336(3):387–93.CrossRefPubMedGoogle Scholar
  15. 15.
    Itahana K, Zhang Y. Mitochondrial p32 is a critical mediator of ARF-induced apoptosis. Cancer Cell. 2008;13(6):542–53.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Reef S, Shifman O, Oren M, Kimchi A. The autophagic inducer smARF interacts with and is stabilized by the mitochondrial p32 protein. Oncogene. 2007;26(46):6677–83.CrossRefPubMedGoogle Scholar
  17. 17.
    Xin T, Zhang F, Jiang Q, Chen C, Huang D, Li Y, et al. Extraction, purification and antitumor activity of a water-soluble polysaccharide from the roots of Polygala tenuifolia. Carbohydr Polym. 2012;90(2):1127–31.CrossRefPubMedGoogle Scholar
  18. 18.
    Rubinstein DB, Stortchevoi A, Boosalis M, Ashfaq R, Ghebrehiwet B, Peerschke EI, et al. Receptor for the globular heads of C1q (gC1q-R, p33, hyaluronan-binding protein) is preferentially expressed by adenocarcinoma cells. Int J Cancer. 2004;110(5):741–50.CrossRefPubMedGoogle Scholar
  19. 19.
    Ghosh I, Chowdhury AR, Rajeswari MR, Datta K. Differential expression of hyaluronic acid binding protein 1 (HABP1)/P32/C1QBP during progression of epidermal carcinoma. Mol Cell Biochem. 2004;267(1–2):133–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Chen YB, Jiang CT, Zhang GQ, Wang JS, Pang D. Increased expression of hyaluronic acid binding protein 1 is correlated with poor prognosis in patients with breast cancer. J Surg Oncol. 2009;100(5):382–6.CrossRefPubMedGoogle Scholar
  21. 21.
    Prakash M, Kale S, Ghosh I, Kundu GC, Datta K. Hyaluronan-binding protein 1 (HABP1/p32/gC1qR) induces melanoma cell migration and tumor growth by NF-kappa B dependent MMP-2 activation through integrin α(v)β(3) interaction. Cell Signal. 2011;23(10):1563–77.CrossRefPubMedGoogle Scholar
  22. 22.
    Yu H, Liu Q, Xin T, Xing L, Dong G, Jiang Q, et al. Elevated expression of hyaluronic acid binding protein 1 (HABP1)/P32/C1QBP is a novel indicator for lymph node and peritoneal metastasis of epithelial ovarian cancer patients. Tumour Biol. 2013;34(6):3981–7.CrossRefPubMedGoogle Scholar
  23. 23.
    Zhao J, Liu T, Yu G, Wang J. Overexpression of HABP1 correlated with clinicopathological characteristics and unfavorable prognosis in endometrial cancer. Tumour Biol. 2014 Oct;30.Google Scholar
  24. 24.
    Alizadeh AA, Ross DT, Perou CM, van de Rijn M. Towards a novel classification of human malignancies based on gene expression patterns. J Pathol. 2001;195(1):41–52.CrossRefPubMedGoogle Scholar
  25. 25.
    Singletary SE, Greene FL. Revision of breast cancer staging: the 6th edition of the TNM classification. Semin Surg Oncol. 2003;21:53–9.CrossRefPubMedGoogle Scholar
  26. 26.
    Kaul R, Saha P, Saradhi M, Prasad RL, Chatterjee S, Ghosh I, et al. Overexpression of hyaluronan-binding protein 1 (HABP1/p32/gC1qR) in HepG2 cells leads to increased hyaluronan synthesis and cell proliferation by up-regulation of cyclin D1 in AKT-dependent pathway. J Biol Chem. 2012;287(23):19750–64.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Zhang X, Zhang F, Guo L, Wang Y, Zhang P, Wang R, et al. Interactome analysis reveals that C1QBP (complement component 1, q subcomponent binding protein) is associated with cancer cell chemotaxis and metastasis. Mol Cell Proteomics. 2013;12(11):3199–209.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Yu G, Wang J. Significance of hyaluronan binding protein (HABP1/P32/gC1qR) expression in advanced serous ovarian cancer patients. Exp Mol Pathol. 2013;94(1):210–5.CrossRefPubMedGoogle Scholar
  29. 29.
    Bialucha CU, Ferber EC, Pichaud F, Peak-Chew SY, Fujita Y. p32 is a novel mammalian Lgl binding protein that enhances the activity of protein kinase Czeta and regulates cell polarity. J Cell Biol. 2007;178(4):575–81.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    von Maltzahn G, Ren Y, Park JH, Min DH, Kotamraju VR, Jayakumar J, et al. In vivo tumor cell targeting with “click” nanoparticles. Bioconjug Chem. 2008;19(8):1570–8.CrossRefGoogle Scholar
  31. 31.
    Saha P, Ghosh I, Datta K. Increased hyaluronan levels in HABP1/p32/gC1qR overexpressing HepG2 cells inhibit autophagic vacuolation regulating tumor potency. PLoS One. 2014;9(7):e103208.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Meenakshi J. Anupama, Goswami SK, Datta K. Constitutive expression of hyaluronan binding protein 1 (HABP1/p32/gC1qR) in normal fibroblast cells perturbs its growth characteristics and induces apoptosis. Biochem Biophys Res Commun. 2003;300(3):686–93.CrossRefPubMedGoogle Scholar
  33. 33.
    Kamal A, Datta K. Upregulation of hyaluronan binding protein 1 (HABP1/p32/gC1qR) is associated with cisplatin induced apoptosis. Apoptosis. 2006;11(5):861–74.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Ji Wang
    • 1
  • Yanni Song
    • 1
  • Tong Liu
    • 1
  • Qingyu Shi
    • 1
  • Zhenbin Zhong
    • 1
  • Wei Wei
    • 1
  • Suyun Huang
    • 2
  • Da Pang
    • 1
    • 3
  1. 1.Department of Breast SurgeryThe Affiliated Tumour Hospital of Harbin Medical UniversityHarbinChina
  2. 2.The University of TexasAnderson Cancer CenterHoustonUSA
  3. 3.Department of Breast SurgeryHeilongjiang Medical Science InstituteHarbinChina

Personalised recommendations