search button

Membrane-bound complement regulatory proteins are prognostic factors of operable breast cancer treated with adjuvant trastuzumab: A retrospective study

  • Authors:
    • Mei Liu
    • Ya-Jun Yang
    • Hong Zheng
    • Xiao-Rong Zhong
    • Yu Wang
    • Zhu Wang
    • Yao-Geng Wang
    • Yan-Ping Wang

  • View Affiliations

  • Published online on: September 18, 2014     https://doi.org/10.3892/or.2014.3496
  • Pages: 2619-2627
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Complement-dependent cytotoxicity (CDC) is an important antitumor mechanism of monoclonal antibodies (mAbs). However, trastuzumab, an anti-HER2 mAb, exerts only minor CDC. Overexpression of membrane-bound complement regulatory proteins (mCRPs), which suppress CDC, have been implicated in various malignant tumors. Here, we explored the predictive role of the expression levels of three mCRPs (CD55, CD59 and CD46) in the prognosis of breast cancer cases that underwent adjuvant trastuzumab treatment. We also studied the effect of mCRP downregulation on trastuzumab-induced CDC in vitro. Sixty-five HER2-positive breast cancer patients who received adjuvant therapy containing trastuzumab, were retrospectively analyzed. Levels of CD55, CD59 and CD46 expression were detected by immunohistochemistry. Chi-square test, Kaplan‑Meier survival analysis and a Cox proportional hazards model were used to analyze the association between CD55, CD59 and CD46 expression and prognosis. HER2-positive SK-Br3 and BT-474 breast cancer cells were pretreated with various drugs to reduce mCRP expression. Afterwards, trastuzumab‑mediated cytolytic effects were measured. Among the 65 patients, 46.2% had high expression of CD55, 44.6% had high expression of CD59 and 44.6% had high expression of CD46. The median follow-up duration was 47 months (range from 24 to 75 months). Patients with CD55 or CD59 overexpression had a higher relapse rate than those with low expression of CD55 (33.3 vs. 8.6%; P=0.013) or CD59 (31.0 vs. 11.1%; P=0.046). Similarly, mean disease-free survival of patients with CD55 or CD59 overexpression was significantly shorter than those with a low expression of CD55 (56 vs. 70 months; log-rank test, P=0.008) or CD59 (56 vs. 69 months; log-rank test, P=0.033). Multivariate analysis confirmed that CD55, but not CD59, was an independent risk factor of recurrence (HR=4.757; 95% CI, 0.985-22.974; P=0.05). In vitro, we found that tamoxifen inhibited both the protein and mRNA expression levels of CD55, but not CD59 or CD46 in SK-Br3 and BT-474 cells. After pretreatment of tamoxifen, trastuzumab-induced cytolysis was enhanced through CD55 downregulation. In conclusion, CD55 overexpression is an independent risk factor for recurrence in breast cancer patients receiving postoperative adjuvant therapy containing trastuzumab. Combined use of tamoxifen and trastuzumab for HER2-positive breast cancer treatment may enhance the antitumor effects of trastuzumab by elevated CDC, which warrants further study.
View Figures
View References

Related Articles

Journal Cover

December-2014
Volume 32 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

  • Journal Metrics
  • Impact Factor: 3.8
  • Ranked Oncology
    (total number of cites)
  • CiteScore: 8.5
  • CiteScore Rank: Q1: #74/404 Oncology
  • Source Normalized Impact per Paper (SNIP): 0.719
  • SCImago Journal Rank (SJR): 0.864
International Symposium on Molecular Medicine Conference Banner
The Cancer Story
World Congress on Advances in Oncology and International Symposium on Molecular Medicine Conference Banner
World Academy Of Sciences Banner
Heyday Road Banner

0

Copy and paste a formatted citation
x
Spandidos Publications style
Liu M, Yang Y, Zheng H, Zhong X, Wang Y, Wang Z, Wang Y and Wang Y: Membrane-bound complement regulatory proteins are prognostic factors of operable breast cancer treated with adjuvant trastuzumab: A retrospective study. Oncol Rep 32: 2619-2627, 2014.
APA
Liu, M., Yang, Y., Zheng, H., Zhong, X., Wang, Y., Wang, Z. ... Wang, Y. (2014). Membrane-bound complement regulatory proteins are prognostic factors of operable breast cancer treated with adjuvant trastuzumab: A retrospective study. Oncology Reports, 32, 2619-2627. https://doi.org/10.3892/or.2014.3496
MLA
Liu, M., Yang, Y., Zheng, H., Zhong, X., Wang, Y., Wang, Z., Wang, Y., Wang, Y."Membrane-bound complement regulatory proteins are prognostic factors of operable breast cancer treated with adjuvant trastuzumab: A retrospective study". Oncology Reports 32.6 (2014): 2619-2627.
Chicago
Liu, M., Yang, Y., Zheng, H., Zhong, X., Wang, Y., Wang, Z., Wang, Y., Wang, Y."Membrane-bound complement regulatory proteins are prognostic factors of operable breast cancer treated with adjuvant trastuzumab: A retrospective study". Oncology Reports 32, no. 6 (2014): 2619-2627. https://doi.org/10.3892/or.2014.3496