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 identified member of the IQGAP family, may act as a crucial factor in cancer development and progression; however, its clinical value in breast cancer remains unestablished. We explored the correlation between IQGAP3 expression profile and the clinicopathological features in breast cancer.Methods: IQGAP3 mRNA and protein levels were detected in breast cancer cell lines and tumor tissues by real-time PCR and western blotting and compared to the normal control groups. Protein expression of IQGAP3 was also evaluated immunohistochemically in archived paraffin-embedded specimens from 257 breast cancer patients, and the associations between IQGAP3 expression level, clinical characteristics, and prognosis were analyzed. We assessed the relationship between IQGAP3 expression and sensitivity to radiation therapy which was determined by subgroup analysis.Results: IQGAP3 was significantly upregulated in breast cancer cell lines and human tumor tissues at both the mRNA and protein level compared to controls. Additionally, high levels of IQGAP3 expression were detected in 110/257 (42.8%) of archived paraffin-embedded breast cancer specimens. High IQGAP3 expression level 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 expression was an independent prognostic factor among all 257 breast cancer patients in our cohort (p = 0.003, p = 0.001). Subgroup analysis revealed IQGAP3 expression correlated with radioresistance and was also an independent predictor of radiotherapy outcome.Conclusion: Our findings suggest that high IQGAP3 expression predicts poor prognosis and radioresistance in breast cancer. Therefore, IQGAP3 may be a reliable prognostic biomarker in breast cancer and could be used to identify patients who may benefit from radiotherapy.

Comprehensive Analyses of the Immunological and Prognostic Roles of an IQGAP3AR/let-7c-5p/IQGAP3 Axis in Different Types of Human Cancer

“…IQGAP3 silencing has been demonstrated to significantly reduce the proliferation, migration, and invasion ability, and induce apoptosis in pancreatic cancer cell lines ( Xu et al, 2016 ). Zhang et al found that IQGAP3 had high expression in breast cancer tissues and cell lines, and its high expression was correlated with the clinical stage, tumor node metastasis stage, and a poor prognosis ( Hua et al, 2020 ). High expression of IQGAP3 has been observed in colorectal cancer ( Wu et al, 2019 ), hepatocellular carcinoma ( Shi et al, 2017 ), bladder cancer ( Xu et al, 2019 ), and gastric cancer ( Huang et al, 2021 ).…”

hnRNPC Promotes Malignancy in Pancreatic Cancer through Stabilization of IQGAP3

“…IQGAP3 is a GTPase activating protein that has been linked to fundamental cellular processes such as cell proliferation, adhesion, cytoskeletal remodelling, and growth factor regulation [ 33 ]. There has recently been an increase in the number of studies on its role in tumorigenesis of the lungs, colorectum, liver, gastric, and breast [ 33 – 36 ]. Surprisingly, majority of these studies suggest that IQGAP3 modulates tumorigenesis by regulating the EMT and thus controlling tumor metastasis.…”

Role of IQ Motif-Containing GTPase-Activating Proteins in Hepatocellular Carcinoma

“…IQGAP3 has received scant attention despite its discovery in 2007 ( 32 ) and its detection in various organs, including the liver, stomach, ovaries, prostate, breast, pancreas, and lung ( 8 , 33 – 38 ). IQGAP3 is mainly expressed in brain ( 39 ) and is critical for regulation of neurite outgrowth of the neurons ( 32 ).…”

“…Accordingly, IQGAP3 is classified as an oncogene owing to its intimate association with tumorigenesis and metastasis. Its expression is inversely linked with clinical characteristics and survival in most cancers ( 8 , 38 , 41 , 42 ).…”