LRP6 as a biomarker of poor prognosis of breast cancer

Abstract

Background: Recently, low-density lipoprotein receptor (LDLR)-related protein 6 (LRP6) has been the focus of molecular targeted therapy for breast cancer; however, its role in breast cancer is still controversial. The purpose of this study was to investigate the effect of LRP6 overexpression on the prognosis of breast cancer. Methods: We used immunohistochemistry to detect the expression of LRP6 via tissue microarrays in breast cancer samples, Chi-square test analyze the relationship between LRP6 expression and clinicopathological features of breast cancer, the Kaplan-Meier method to perform survival analysis, and the Cox proportional hazards regression model to explore the potential risk factors of breast cancer. The role of LRP6 in the proliferation, invasion, and metastasis of breast cancer was studied by colony formation, Transwell migration and invasion assay and scratch assay. The tumor-bearing model of LRP6 knockdown was established using MCF-7 cells, and corresponding negative control was set up to observe the growth rate of the two models. Results: High expression of LRP6 was observed in 89 out of 150 (59.3%) breast cancer cases, as detected by microarray of breast cancer tissue. Chi-square tests showed no significant correlation between LRP6 expression and tumor size, lymph node staging, or mitosis. Survival analysis showed that the overall survival rate of tumor patients with high LRP6 expression was significantly lower than that of patients with low LRP6 expression. Univariate and multivariate regression analyses revealed that LRP6 was an independent risk factor for breast cancer and was negatively correlated with the prognosis of breast cancer. Compared with the control group, small interference RNA (si-RNA) knockdown of LRP6 significantly reduced the clonogenic rate as well as the migration and invasion abilities of MCF-7 cells. In the scratch experiment, the wound healing ability of the LRP6 knockdown was significantly weaker than that of the control group. There were significant differences in tumor growth weight and volume between lentivirus transfected LRP6 knockdown MCF-7 cell line and control MCF-7 cell line in nude mice. Conclusions: LRP6 could be a useful biomarker of poor prognosis of breast cancer, as it plays an important role in tumor growth, migration, and invasion.