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

Abstract

Background: IQ motif-containing GTPase activating 24 protein 3 (IQGAP3), the latest found protein of IQGAP family, 25 may act as a crucial factor in the process of cancer development 26 and progression; however, its clinical value in breast cancer 27 remains unestablished so far. Our team explored the correlation 28 between IQGAP3 expression profile and the clinicopathological 29 features in breast cancer. Methods: IQGAP3 levels in breast 30 cancer cell lines and tumor tissues were detected by real-time 31 PCR and western blotting and compared to the normal control 32 groups. Protein expression of IQGAP3 was evaluated 33 immunohistochemically in specimens (archived paraffin 34 embedded) of 257 breast cancer patients. We also analyze the 35 association between IQGAP3 expression and the clinical 36 characters and prognosis. The relationship between IQGAP3 37 expression and sensitivity to radiation therapy was determined 38 by subgroup analysis. Results: There was significant 39 upregulation of IQGAP3 in breast cancer cell lines and human 40 tumor tissues at both the mRNA and protein level compared to 41 the normal ones. In addition, 110/257 (42.8%) of archived 42 paraffin embedded breast cancer specimens had high protein 43 expression of IQGAP3. High expression of IQGAP3 was 44 significantly related to clinical stage (P=0.001), T category 45 (P=0.002), N category (P=0.001), locoregional 46 recurrence(P=0.002), distant metastasis (P=0.001), and vital 47 status (P=0.001). Univariate and multivariate statistical analysis 48showed that IQGAP3 was an independent prognostic factor of 49 the whole cohort breast cancer patients (P=0.003, P=0.001). 50Subgroup analysis revealed IQGAP3 expression correlates with 51 radiation therapy resistance and was also an independent 52 predictor for radiation therapy outcome. Conclusions: Our 53 findings suggest that high IQGAP3 expression predicts poor 54 prognosis and radiation therapy resistance in breast cancer. In 55 addition, IQGAP3 may be a reliable novel biomarker to provide 56 personalized prognostication and identify patients who can 57 profit from more aggressive RT regimen for improving the 58 survival of breast cancer patients. 59 1. Introduction 62 Breast cancer is the most frequent malignancy in women and the 63 second leading cause of cancer-related deaths worldwide[1]. Radiation 64 therapy (RT) is an indispensable part of the systemic therapeutic regimen 65 of breast cancer. Despite great progress in RT over recent years, 66 locoregional recurrence and distant metastasis after RT remain key 67 problems decreasing the survival of breast cancer patients [2]. 68 Locoregional recurrence results from the presence or evolution of 69 radioresistant tumor cells for which standard fractionated RT doses are 70 sublethal[3]. Currently, there is a dearth of clinically available 71 predictive biomarkers to indicate the optimal radiation dosing in breast 72 cancer, which leads to suboptimal treatment of these patients[4]. 73 Therefore, further researches to identify novel biomarkers a...

IQ Motif Containing GTPase-Activating Protein 3 (IQGAP3) Inhibits Kaempferol-Induced Apoptosis in Breast Cancer Cells by Extracellular Signal-Regulated Kinases 1/2 (ERK1/2) Signaling Activation

“…IQGAP3 is a newly discovered IQGAP and has been found to be overexpressed in BC tissues in our previous studies [20,32]. In the present study, we found that the high expression of IQGAP3 in BC cells was significantly reduced by natural phytochemicals, especially Kaempferol.…”

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

“…This manuscript has been released as a preprint at bioRxiv ( Hua et al, 2018 ) and the abstract of this manuscript has been accepted as an oral presentation in ESMO ASIA annual meeting 2018. We would like to thank the native English speaking scientists of Elixigen Company (Huntington Beach, California) for editing our manuscript.…”