Prognostic value of MET protein overexpression and gene amplification in locoregionally advanced nasopharyngeal carcinoma.
Prognostic value of MET protein overexpression and gene amplification in locoregionally advanced nasopharyngeal carcinoma.
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MET蛋白过表达和基因扩增在局部晚期鼻咽癌中的预后价值
DOI：
10.18632/oncotarget.3751
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发表时间：
2015-05-30
期刊：
影响因子：
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通讯作者：
Ma J
中科院分区：
文献类型：
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作者：
Li Y;Li W;He Q;Xu Y;Ren X;Tang X;Wen X;Yang X;Sun Y;Zeng J;Yun J;Liu N;Ma J
本研究评估MET蛋白过表达和基因扩增在局部区域晚期鼻咽癌（NPC）中的发生率和预后价值。对连续376例局部晚期鼻咽癌患者的标本进行免疫组织化学分析MET蛋白表达和荧光原位杂交评估MET扩增状态。376例患者中有139例（37.0%）MET蛋白过表达；其中7/139（5.0%）有MET扩增。MET过表达与局部区域失败（P = 0.009）、远处转移（P = 0.006）和死亡（P < 0.001）显著相关；MET扩增与死亡显著相关（P = 0.021）。MET拷贝数状态与MET蛋白表达呈正相关（r = 0.629, P < 0.001）。多因素分析显示MET过表达是总生存（OS， HR, 1.99; 95% CI, 1.38-2.87; P < 0.001）和无病生存（DFS， HR, 1.85; 95% CI, 1.33-2.57; P < 0.001）的独立预后因素，MET扩增与较差的OS （HR, 4.24; 95% CI, 1.78-10.08; P < 0.001）和DFS （HR, 5.44; 95% CI, 2.44-12.09; P < 0.001）独立相关。综上所述，MET蛋白过表达和基因扩增是局部区域晚期鼻咽癌OS和DFS的独立预后因素，可能为识别MET抑制剂可能有益的患者提供治疗性生物标志物。
This study assessed the incidence and prognostic value of MET protein overexpression and gene amplification in locoregionally advanced nasopharyngeal carcinoma (NPC). Specimens from 376 consecutive patients with locoregionally advanced NPC were subjected to immunohistochemistry to analyze MET protein expression and fluorescence in situ hybridization to assess MET amplification status. In total, 139/376 (37.0%) patients had MET protein overexpression; of whom, 7/139 (5.0%) had MET amplification. MET overexpression was significantly associated with locoregional failure (P = 0.009), distant metastasis (P = 0.006) and death (P < 0.001); MET amplification was significantly associated with death (P = 0.021). A positive correlation was observed between MET copy number status and MET protein expression (r = 0.629, P < 0.001). Multivariate analysis demonstrated MET overexpression was an independent prognostic factor for overall survival (OS; HR, 1.99; 95% CI, 1.38–2.87; P < 0.001) and disease-free survival (DFS; HR, 1.85; 95% CI, 1.33–2.57; P < 0.001), and MET amplification was independently associated with poorer OS (HR, 4.24; 95% CI, 1.78-10.08; P < 0.001) and DFS (HR, 5.44; 95% CI, 2.44-12.09; P < 0.001). In conclusion, MET protein overexpression and gene amplification are independent prognostic factors for OS and DFS in locoregionally advanced nasopharyngeal carcinoma, and may provide therapeutic biomarkers to identify patients in whom MET inhibitors may be beneficial.