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

EGFR 高表达预示切除的 T3 期胃腺癌患者生存率低,并促进癌细胞存活

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

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=3.10×10-9 and P=6.74×10-8, 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=2.37×10-8 and HR, 1.80; 95% CI, 1.50-2.17; P=3.80×10-10]. 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.

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