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Legumain Protein as a Potential Predictive Biomarker for Asian Patients with Breast Carcinoma

  • Wu, Mei ;
  • Shao, Guang-Rui ;
  • Zhang, Fei-Xue ;
  • Wu, Wen-Xiu ;
  • Xu, Ping ;
  • Ruan, Zheng-Min
  • Published : 2015.01.22

Abstract

Background: Treatment for breast cancer is mainly performed by surgical resection of primary tumors and chemotherapy. However, after tumor invasion and metastases, breast cancer is hard to control. Clarification of the pathogenic mechanisms would be helpful to the prognosis or therapy for the breast cancer. The aim of this study is to investigate the clinical and prognostic implications of legumain protein Materials and Methods: In this study, we examined mastectomy specimens from 114 breast cancer and matching, 26 adjacent non-cancerous tissues using immunohistochemistry. Results: The results indicated that positive expression of legumain protein in breast cancer was 51.8 % (59/114) and the positive expression of legumain protein in adjacent non-cancerous tissue was 11.5% (3/26). It appeared to be related with lymph node metastasis of breast cancer (p=0.02) and correlation analysis indicated that legumain expression was correlated positively with the estrogen receptor (ER) and mutant-type p53 expression (both p<0.05). Positive legumain expression was significantly associated with shorter overall survival time in breast cancer patients (log-rank p<0.01). Multivariate survival analysis suggested that the positive legumain expression was an independent predictor of poorer overall survival in patients with breast cancer (HR=0.24; 95%CI 0.11-0.65, p=0.03). Conclusions: Legumain might be a new potential biomarker for breast cancer, which may reflect the prognosis and overall survival.

Keywords

Breast cancer;legumain;prognostic biomarker;positive expression

References

  1. Asiaf A, Ahmad ST, Aziz SA, et al (2014). Loss of expression and abberrant methylation of the CDH1 (E-cadherin) gene in breast cancer patients from Kashmir. Asian Pac J Cancer Prev, 15, 6397-403. https://doi.org/10.7314/APJCP.2014.15.15.6397
  2. Casas A, Llombart A, Martin M (2013). Denosumab for the treatment of bone metastases in advanced breast cancer. Breast, 22, 585-92. https://doi.org/10.1016/j.breast.2013.05.007
  3. Chen JM, Fortunato M, Stevens RA, et al (2001). Activation of progelatinase A by mammalian legumain, a recently discovered cysteine proteinase. Biol Chem, 382, 77-83.
  4. Elzawawy A (2008). Breast cancer systemic therapy: the need for more economically sustainable scientific strategies in the world. Breast Care, 3, 434-8.
  5. Gawenda J, Traub F, Luck HJ, et al (2007). Legumain expression as a prognostic factor in breast cancer patients. Breast Cancer Res Treat, 102, 1-6. https://doi.org/10.1007/s10549-006-9311-z
  6. Guo P, Zhu A, Sun Z, et al (2013). Expression of legumain correlates with prognosis and metastasis in gastric carcinoma. PLoS One, 8, 73090. https://doi.org/10.1371/journal.pone.0073090
  7. Hu Q, Luo Z, Xu T, et al (2014). FOXA1: a promising prognostic marker in breast cancer. Asian Pac J Cancer Prev, 15, 11-6. https://doi.org/10.7314/APJCP.2014.15.1.11
  8. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  9. Lewen A, Zhou H, Hu HD, et al (2008). A legumain-based minigene vaccine targets the tumor stroma and suppresses breast cancer growth and angiogenesis. Cancer Immunol Immunother, 57, 507-15. https://doi.org/10.1007/s00262-007-0389-x
  10. Liu C, Sun X, Huang H, et al (2003). Overexpression of legumain in tumors is significant for invasion/metastasis and a candidate enzymatic target for prodrug therapy. Cancer Res, 63, 2957-64.
  11. Luo Y, Zhou H, Krueger J, et al (2006). Targeting tumor-associated macrophages as a novel strategy against breast cancer. J Clin Invest, 116, 2132-41. https://doi.org/10.1172/JCI27648
  12. Murthy RV, Arbman G, Gao J, et al (2005). Legumain expression in relation to clinicopathologic and biological variables in colorectal cancer. Clin Cancer Res, 11, 2293-9. https://doi.org/10.1158/1078-0432.CCR-04-1642
  13. Parajuly SS, Lan PY, Yu MB, et al (2012). Diagnostic potential of strain ratio measurement and a 5 point scoring method for detection of breast cancer: Chinese experience. Asian Pac J Cancer Prev, 13, 1447-52. https://doi.org/10.7314/APJCP.2012.13.4.1447
  14. Reisfeld RA (2013). The tumor microenvironment: a target for combination therapy of breast cancer. Crit Rev Oncog, 18, 115-33. https://doi.org/10.1615/CritRevOncog.v18.i1-2.70
  15. Rustogi A, Budrukkar A, Dinshaw K, et al (2005). Management of locally advanced breast cancer: evolution and current practice. J Cancer Res Ther, 1, 21-30. https://doi.org/10.4103/0973-1482.16086
  16. Santamaria ME, Hernandez-Crespo P, Ortego F, et al (2012). Cysteine peptidases and their inhibitors in Tetranychus urticae: a comparative genomic approach. BMC Genomics, 13, 307. https://doi.org/10.1186/1471-2164-13-307
  17. Sevenich L, Schurigt U, Sachse K, et al (2010). Synergistic antitumor effects of combined cathepsin B and cathepsin Z deficiencies on breast cancer progression and metastasis in mice. Proc Natl Acad Sci USA, 107, 2497-502. https://doi.org/10.1073/pnas.0907240107
  18. Taib NA, Akmal M, Mohamed I, Yip CH. (2011). Improvement in survival of breast cancer patients- trends over time periods in a single institution in an Asian Pacific country, Malaysia. Asian Pac J Cancer Prev, 12, 345-9.
  19. Velaiutham S, Taib NA, Ng KL, Yoong BK, Yip CH (2008). Does the pre-operative value of serum CA15-3 correlate with survival in breast cancer. Asian Pac J Cancer Prev, 9, 445-8.
  20. Wang L, Chen S, Zhang M, et al (2012). Legumain: a biomarker for diagnosis and prognosis of human ovarian cancer. J Cell Biochem, 113, 2679-86. https://doi.org/10.1002/jcb.24143
  21. Wu W, Luo Y, Sun C, et al (2006). Targeting cell-impermeable prodrug activation to tumor microenvironment eradicates multiple drug-resistant neoplasms. Cancer Res, 66, 970-80. https://doi.org/10.1158/0008-5472.CAN-05-2591

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  1. MiRNA-Embedded ShRNAs for Radiation-Inducible LGMN Knockdown and the Antitumor Effects on Breast Cancer vol.11, pp.9, 2016, https://doi.org/10.1371/journal.pone.0163446
  2. Legumain is an independent predictor for invasive recurrence in breast ductal carcinoma in situ pp.1530-0285, 2018, https://doi.org/10.1038/s41379-018-0180-x