Elevated expression of IRS-1 associates with phosphorylated Akt expression and predicts poor prognosis of breast invasive ductal carcinoma
Elevated expression of IRS-1 associates with phosphorylated Akt expression and predicts poor prognosis of breast invasive ductal carcinoma
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IRS-1 表达升高与磷酸化 Akt 表达相关，可预测乳腺浸润性导管癌的不良预后
DOI：
10.1016/j.humpath.2018.03.003
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发表时间：
2018-09-01
期刊：
影响因子：
3.3
通讯作者：
Chu, Shuzhou
中科院分区：
文献类型：
--
作者：
Luo, Jiadi;Feng, Juan;Chu, Shuzhou
据报道，胰岛素受体底物1 （IRS-1）的过表达可促进细胞生长、非典型增生和癌变，磷酸化Akt （p-Akt）被证实参与多种类型的癌症，如乳腺浸润性导管癌（BIDC）。然而，IRS-1与Akt的关系以及IRS-1表达在BIDC中的作用尚未报道。本研究旨在通过免疫组化研究IRS-1和p-Akt蛋白表达与BIDC临床病理特征及生存状况的关系。结果显示，与非癌患者对照乳腺组织相比，BIDC中IRS-1表达升高或P - akt表达阳性的比例均显著高于对照组（P < 0.001和P = 0.001）。IRS-1过表达与P - akt阳性表达显著相关（0.337,P < 0.001）。P - akt的阳性表达率在不同分子亚型的BIDC中也有统计学差异（在luminal B BIDC中最高，P = 0.009）。此外，IRS-1和P - akt高表达的BIDC患者的总生存率明显低于低表达的患者（P = 0.006和P = 0.004）。多因素Cox比例风险回归分析显示，IRS-1高表达和P - akt蛋白阳性表达是BIDC患者预后不良的独立因素（P = 0.022和P = 0.046）。综上所述，我们首次报道了IRS-1蛋白的过表达与p-Akt的表达相关，1RS-1的过表达和p-Akt的阳性表达可能是BIDC不良预后的独立生物标志物。(C) 2018爱思唯尔公司版权所有。
Overexpression of insulin receptor substrate 1 (IRS-1) has been reported to promote cell growth, atypical hyperplasia, and carcinogenesis, and phosphorylated Akt (p-Akt) is certified to be involved in many types of cancers such as breast invasive ductal carcinoma (BIDC). However, the relationship between IRS-1 and Akt, as well as the role of expression of IRS-1 in BIDC, has never been reported. The purpose of this research is to investigate the association between expression of IRS-1 and p-Akt proteins and clinicopathological features of BIDC by immunohistochemistry, as well as the survival status. The results showed that the percentage of either elevated expression of IRS-1 or positive p-Akt expression in BIDC was significantly higher than that in control breast tissue from noncancer patients (P < .001 and P = .001, respectively). Overexpression of IRS-1 was evidently associated with positive expression of p-Akt = 0.337, P < .001). Also, positive percentage of p-Akt expression was statistically different among different molecular subtypes of BIDC (highest in luminal B BIDC, P = .009). Furthermore, significantly worse overall survival was found in BIDC patients with high expression of IRS-1 and p-Akt than in patients with low expression (P = .006 and P = .004, respectively). The multivariate Cox proportional hazard regression analysis showed that high expression of IRS-1 and positive expression of p-Akt protein were independent poor prognostic factors for patients with BIDC (P = .022 and P = .046, respectively). In conclusion, we report for the first time that overexpression of IRS-1 protein is associated with expression of p-Akt, and overexpression of 1RS-1 and positive expression of p-Akt might be independent biomarkers for poor prognosis in BIDC. (C) 2018 Elsevier Inc. All rights reserved.