IQGAP3 Overexpression Correlates with Poor Prognosis and Radiation Therapy Resistance in Breast Cancer

Abstract

Background: IQ motif-containing GTPase activating protein 3 (IQGAP3), the latest found protein of IQGAP family, 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 IQGAP3 expression profile and the clinicopathological features in breast cancer. Methods: IQGAP3 levels in breast cancer cell lines and tumor tissues were detected by real-time PCR and western blotting and compared to the normal control groups. Protein expression of IQGAP3 was evaluated immunohistochemically in specimens (archived paraffin embedded) of 257 breast cancer patients. We also analyze the association between IQGAP3 expression and the clinical characters and prognosis. The relationship between IQGAP3 expression and sensitivity to radiation therapy was determined by subgroup analysis. Results: There was significant upregulation of IQGAP3 in breast cancer cell lines and human tumor tissues at both the mRNA and protein level compared to the normal ones. In addition, 110/257 (42.8%) of archived paraffin embedded breast cancer specimens had high protein expression of IQGAP3. High expression of IQGAP3 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 analysis showed that IQGAP3 was an independent prognostic factor of the whole cohort breast cancer patients (P=0.003, P=0.001). Subgroup analysis revealed IQGAP3 expression correlates with radiation therapy resistance and was also an independent predictor for radiation therapy outcome. Conclusions: Our findings suggest that high IQGAP3 expression predicts poor prognosis and radiation therapy resistance in breast cancer. In addition, IQGAP3 may be a reliable novel biomarker to provide personalized prognostication and identify patients who can profit from more aggressive RT regimen for improving the survival of breast cancer patients.