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表皮生长因子受体(EGFR)的高表达预示着接受手术切除的T3期胃腺癌患者预后不良,并促进癌细胞存活。

High expression of EGFR predicts poor survival in patients with resected T3 stage gastric adenocarcinoma and promotes cancer cell survival.

作者信息

Wang Daiyong, Wang Bing, Wang Ruohan, Zhang Zaizhong, Lin Youdong, Huang Guoliang, Lin Songbin, Jiang Yifan, Wang Wenyuan, Wang Lie, Huang Qiaojia

机构信息

Department of General Surgery, Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350025, P.R. China.

Department of General Surgery, Fuzhou General Hospital, Dongfang Hospital, Fuzhou, Fujian 350025, P.R. China.

出版信息

Oncol Lett. 2017 May;13(5):3003-3013. doi: 10.3892/ol.2017.5827. Epub 2017 Mar 8.

Abstract

Epidermal growth factor receptor (EGFR) is an essential regulator and biomarker of several types of cancer. However, the association between its expression and prognosis in patients with resected T3 stage gastric adenocarcinoma (RT3-GA) remains to be determined. In total, 683 patients with resectable T3-GA who underwent surgery were retrospectively included in the present study, and their immunohistochemical data for EGFR expression were collected. The associations between the patients' clinicopathologic characteristics and EGFR immunohistochemistry data were analyzed by multiple statistical methods. Annexin V apoptosis and MTT cell viability assays were performed to explore the effect of EGFR on AGS gastric adenocarcinoma cell survival. EGFR expression levels were categorized into two groups: low (406 cases) and high (277 cases). High EGFR was demonstrated to be significantly associated with distant metastasis (P=0.043) and severely decreased median overall survival time (MOST) and recurrence-free survival time (MRFST). MOST and MRFST in the low EGFR group were 39 and 37 months, respectively; whereas in the high EGFR group these values were only 18 and 13 months (P=3.10×10 and P=6.74×10, respectively). Multivariate analysis confirmed that high EGFR expression levels were associated with poor survival, which was associated with significantly increased recurrence risk and ~2-fold elevation in mortality risk [hazard ratio (HR), 1.73; 95% confidence interval (CI), 1.43-2.10; P=2.37×10 and HR, 1.80; 95% CI, 1.50-2.17; P=3.80×10]. Inhibiting EGFR with AG1478 suppressed its effect on promoting AGS cell survival. These results suggest that high EGFR expression indicates poor survival in patients with RT3-GA, which may be correlated with EGFR promoting GA cell survival.

摘要

表皮生长因子受体(EGFR)是多种癌症的重要调节因子和生物标志物。然而,其表达与T3期胃腺癌(RT3-GA)切除患者预后之间的关联仍有待确定。本研究共回顾性纳入683例行手术切除的可切除T3-GA患者,并收集其EGFR表达的免疫组化数据。采用多种统计方法分析患者临床病理特征与EGFR免疫组化数据之间的关联。进行膜联蛋白V凋亡和MTT细胞活力测定,以探讨EGFR对AGS胃腺癌细胞存活的影响。EGFR表达水平分为两组:低表达组(406例)和高表达组(277例)。结果显示,高EGFR表达与远处转移显著相关(P=0.043),且严重缩短了中位总生存时间(MOST)和无复发生存时间(MRFST)。低EGFR组的MOST和MRFST分别为39个月和37个月;而高EGFR组的这些值仅为18个月和13个月(P分别为3.10×10和6.74×10)。多因素分析证实,高EGFR表达水平与生存不良相关,这与复发风险显著增加和死亡风险升高约2倍有关[风险比(HR),1.73;95%置信区间(CI),1.43-2.10;P=2.37×10;HR,1.80;95%CI,1.50-2.17;P=3.80×10]。用AG1478抑制EGFR可抑制其对AGS细胞存活的促进作用。这些结果表明,高EGFR表达表明RT3-GA患者生存不良,这可能与EGFR促进GA细胞存活有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6495/5431275/18607adf675e/ol-13-05-3003-g00.jpg

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