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表皮生长因子受体(EGFR)和磷酸化蛋白激酶B(p-AKT)过表达对胃癌染色体不稳定性的影响

Effect of EGFR and p-AKT Overexpression on Chromosomal Instability in Gastric Cancer.

作者信息

Hisamatsu Yuichi, Oki Eiji, Otsu Hajime, Ando Koji, Saeki Hiroshi, Tokunaga Eriko, Aishima Shinichi, Morita Masaru, Oda Yoshinao, Maehara Yoshihiko

机构信息

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Department Anatomic Pathology and Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

出版信息

Ann Surg Oncol. 2016 Jun;23(6):1986-92. doi: 10.1245/s10434-016-5097-3. Epub 2016 Feb 4.

Abstract

BACKGROUND

Molecular profiling in gastric cancer (GC) is important for diagnosis and treatment. In this study, we investigated signal transduction pathways that might induce chromosomal instability in GC.

METHODS

Epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and p-AKT expression were analyzed using immunohistochemistry, and chromosomal instability was assessed by DNA aneuploidy using laser scanning cytometry, in a total of 202 GC cases.

RESULTS

The rate of EGFR expression and p-AKT expression was 70.3 and 34.2 %, respectively, in GC patients. In total, 57.5 % of GC patients exhibited DNA aneuploidy, and p-AKT positively correlated with EGFR and HER2 (p = 0.0127 and p = 0.00031, respectively). Patients with EGFR overexpressing GC showed shorter disease-specific survival than the other cases (hazard ratio 2.00, 95 % confidence interval 1.19-3.53; p = 0.0104). Moreover, EGFR and p-AKT expression was significantly correlated with DNA aneuploidy (p = 0.0002 and p = 0.0302, respectively).

CONCLUSIONS

Our data showed that both EGFR and p-AKT overexpression were clearly associated with DNA aneuploidy. Aneuploidy could be a useful marker for therapies that target EGFR.

摘要

背景

胃癌(GC)的分子谱分析对诊断和治疗很重要。在本研究中,我们调查了可能诱导胃癌染色体不稳定的信号转导通路。

方法

采用免疫组织化学分析表皮生长因子受体(EGFR)、人表皮生长因子受体2(HER2)和p-AKT的表达,并使用激光扫描细胞术通过DNA非整倍体评估染色体不稳定性,共纳入202例胃癌病例。

结果

胃癌患者中EGFR表达率和p-AKT表达率分别为70.3%和34.2%。总体而言,57.5%的胃癌患者表现出DNA非整倍体,p-AKT与EGFR和HER2呈正相关(分别为p = 0.0127和p = 0.00031)。EGFR过表达的胃癌患者的疾病特异性生存期短于其他病例(风险比2.00,95%置信区间1.19 - 3.53;p = 0.0104)。此外,EGFR和p-AKT表达与DNA非整倍体显著相关(分别为p = 0.0002和p = 0.0302)。

结论

我们的数据表明,EGFR和p-AKT过表达均与DNA非整倍体明显相关。非整倍体可能是靶向EGFR治疗的有用标志物。

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