IQ Motif-Containing GTPase-Activating Protein 3 Overexpression Correlates with Poor Prognosis and Radiation Therapy Resistance in Breast Cancer

Abstract

IQ motif-containing GTPase-activating protein 3 (IQGAP3), the latest found IQGAP family protein, may act as a crucial factor in the process of cancer development and progression; however, its clinical value in breast cancer remains unestablished so far. Our team explored the correlation between the IQGAP3 expression profile and clinicopathological features in breast cancer. IQGAP3 levels in breast cancer cell lines and tumor tissues were detected through real-time PCR and western blotting. We evaluated IQGAP3 expression in archived paraffin-embedded tissue specimens of 257 breast cancer patients, and determined the relationship between IQGAP3 expression and sensitivity to radiation therapy (RT), using subgroup analysis. We also analyzed the association between IQGAP3 expression and the clinical characters and prognosis of breast cancer. There was a significant upregulation of IQGAP3 in breast cancer cell lines and human tumor tissues at both mRNA and protein levels. In addition, 42.8% of the breast cancer specimens had high expression of IQGAP3, which was significantly related to clinical stage (P = 0.001), T category (P = 0.002), N category (P = 0.001), locoregional recurrence (P = 0.002), distant metastasis (P = 0.001), and vital status (P = 0.001). Univariate and multivariate statistical analyses showed that IQGAP3 is an independent prognostic factor for all the breast cancer patients (P = 0.003, P = 0.001). Subgroup analysis revealed that IQGAP3 expression is correlated with radiation therapy resistance and is an independent predictor for radiation therapy outcome. Our findings suggest that IQGAP3 may be a reliable novel biomarker to provide personalized prognosis and identify patients who can profit from a more aggressive RT regimen for improving breast cancer patient survival.