Expression of XB130 in human ductal breast cancer

Int J Clin Exp Pathol. 2015 May 1;8(5):5300-8. eCollection 2015.

Abstract

Objectives: XB130 is involved in gene regulation, cell proliferation, cell survival, cell migration, and tumorigenesis. In the present study, we first evaluated the expression of the XB130 and its prognostic significance in breast cancer. Then we evaluated whether XB130 could be a target for therapy in breast cancer.

Materials and methods: Immunohistochemistry was used to assess the level of XB130 protein in surgically resected, formalin-fixed, paraffin-embedded breast cancer specimens. Associations between XB130 and the postoperative prognosis of patients with breast cancer were evaluated. We evaluated the effect of XB130 inhibited by RNA interference on proliferation, invasion and apoptosis in vitro in a metastatic subclone of MCF-7 breast cancer cell line (LM-MCF-7). The effect of XB130 silencing alone or in combination with gemcitabine on LM-MCF-7 cells apoptosis was also investigated.

Results: XB130 protein was present in the cytoplasm of malignant cells, and not in the normal breast tissues. There was correlation between the presence of XB130 in tumour cells and lymph node status, tumor classification and clinical stage. XB130 expression level was significantly associated with recurrence-free and overall survival. Furthermore, multivariate Cox regression analyses revealed that positive XB130 was an independent risk factor for overall survival and recurrence free survival. XB130 silencing alone inhibits tumor growth and induces apoptosis in the LM-MCF-7 cells. Depletion of the XB130 in combination with gemcitabine resulted in marked apoptotic and necrotic cell death in LM-MCF-7 cells.

Conclusions: XB130 could be useful as a prognostic marker of recurrence-free and overall survival in invasive breast cancer, as well as for the response to chemotherapy.

Keywords: Breast cancer; XB130; apoptosis; gemcitabine; invasion.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Antimetabolites, Antineoplastic / pharmacology
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / metabolism*
  • Carcinoma, Ductal, Breast / mortality
  • Carcinoma, Ductal, Breast / secondary
  • Carcinoma, Ductal, Breast / therapy
  • Cell Movement
  • Cell Proliferation
  • Chi-Square Distribution
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Disease-Free Survival
  • Female
  • Gemcitabine
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • MCF-7 Cells
  • Mastectomy
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Proportional Hazards Models
  • RNA Interference
  • Risk Factors
  • Signal Transduction
  • Time Factors
  • Transfection
  • Treatment Outcome
  • Up-Regulation

Substances

  • AFAP1L2 protein, human
  • Adaptor Proteins, Signal Transducing
  • Antimetabolites, Antineoplastic
  • Biomarkers, Tumor
  • Deoxycytidine
  • Gemcitabine