Increased levels of LAPTM4B, VEGF and survivin are correlated with tumor progression and poor prognosis in breast cancer patients

Oncotarget. 2017 Jun 20;8(25):41282-41293. doi: 10.18632/oncotarget.17176.

Abstract

Objective: This study explored the relationships among the expression of LAPTM4B, VEGF, and survivin and clinicopathological characteristics and prognosis in breast cancer patients.

Methods: The expression of these three molecules in 110 stage I-III breast cancer patients with clinicopathological and follow-up data was detected via immunohistochemistry. Kaplan-Meier and Cox proportional hazard regression analyses were performed to assess the prognostic significance of these markers in breast cancer. Moreover, expression levels of these markers were evaluated in 5 breast cell lines via Western blot analysis.

Results: LAPTM4B, VEGF, and survivin were over-expressed in breast cancer specimens and highly expressed in MDA-MB-231 cells. VEGF and nuclear survivin expression was significantly correlated with LAPTM4B expression, and high levels of all three were associated with a tumor size >2cm, TNM stage II+III and lymph node metastasis, which had worse impacts on overall survival and progression-free survival in breast cancer patients. A multivariate Cox analysis identified LAPTM4B over-expression as an independent prognostic marker in breast cancer.

Conclusions: These findings suggest that LAPTM4B, VEGF, and nuclear survivin expression are significantly correlated in breast cancer, which may be predictive of prognosis as well as effective therapeutic targets for new anticancer therapies.

Keywords: LAPTM4B; VEGF; breast cancer; prognosis; survivin.

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Disease Progression
  • Humans
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Oncogene Proteins / metabolism*
  • Prognosis
  • Survivin
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • BIRC5 protein, human
  • Biomarkers, Tumor
  • Inhibitor of Apoptosis Proteins
  • LAPTM4B protein, human
  • Membrane Proteins
  • Oncogene Proteins
  • Survivin
  • Vascular Endothelial Growth Factor A