IQGAP3 Overexpression Correlates With Poor Prognosis and Radiation Therapy Resistance in Breast Cancer.
IQGAP3 Overexpression Correlates With Poor Prognosis and Radiation Therapy Resistance in Breast Cancer.
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IQGAP3 过度表达与乳腺癌不良预后和放射治疗耐药性相关
DOI：
10.3389/fphar.2020.584450
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发表时间：
2020
影响因子：
5.6
通讯作者：
Zhang WW
中科院分区：
文献类型：
--
作者：
Hua X;Long ZQ;Guo L;Wen W;Huang X;Zhang WW
背景：IQ基序-含GTPase激活蛋白3 （IQGAP3）是最新发现的IQGAP家族成员，可能在癌症发生和进展中起关键作用；然而，其在乳腺癌中的临床价值尚未确定。我们探讨了IQGAP3表达谱与乳腺癌临床病理特征的相关性。方法：采用实时荧光定量PCR和western blotting检测乳腺癌细胞系和肿瘤组织中IQGAP3 mRNA和蛋白水平，并与正常对照组进行比较。通过免疫组织化学方法对257例乳腺癌石蜡包埋标本中IQGAP3蛋白表达进行检测，分析IQGAP3表达水平与临床特征及预后的关系。我们通过亚组分析评估了IQGAP3表达与放射治疗敏感性之间的关系。结果：与对照组相比，IQGAP3在乳腺癌细胞系和人肿瘤组织中mRNA和蛋白水平均显著上调。此外，在保存的石蜡包埋乳腺癌标本中，110/257（42.8%）检测到高水平的IQGAP3表达。IQGAP3高表达水平与临床分期（p = 0.001）、T分型（p = 0.002）、N分型（p = 0.001）、局部复发（p = 0.002）、远处转移（p = 0.001）、生命体征（p = 0.001）相关。单因素和多因素统计分析显示，在本组257例乳腺癌患者中，IQGAP3表达是独立的预后因素（p = 0.003, p = 0.001）。亚组分析显示IQGAP3表达与放疗耐药相关，也是放疗结果的独立预测因子。结论：IQGAP3高表达与乳腺癌预后不良及放疗耐药有关。因此，IQGAP3可能是一种可靠的乳腺癌预后生物标志物，可用于识别可能从放疗中受益的患者。
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.
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