Abstract
ObjectiveThis study explored the relationships among the expression of LAPTM4B, VEGF, and survivin and clinicopathological characteristics and prognosis in breast cancer patients.MethodsThe 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.ResultsLAPTM4B, 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.ConclusionsThese 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.
Highlights
Breast cancer is one of the most common cancers among women, and epidemiological statistics show that the incidence of this disease and its associated mortality are increasing yearly [1]
Lysosome-associated protein transmembrane-4 beta (LAPTM4B), Vascular endothelial growth factor (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
Summary
Breast cancer is one of the most common cancers among women, and epidemiological statistics show that the incidence of this disease and its associated mortality are increasing yearly [1]. Previous studies showed that LAPTM4B-35 activity was elevated in various malignant tumors, which was associated with poor prognosis [4,5,6]. It was indicated that LAPTM4B could increase the proliferation and metastasis of tumor cells, reduce apoptosis, and assist drug resistance, which involved in activated PI3K/AKT and Ras-MAPK signaling pathways [7]. Angiogenesis is an important feature of carcinogenesis, progression and metastasis in many human malignancies. Vascular endothelial growth factor (VEGF) is thought to be a major mediator of angiogenesis that promotes the proliferation of tumor cells and boosts www.impactjournals.com/oncotarget
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