Li Yingqin, Li Wenfei, He Qingmei, Xu Yafei, Ren Xianyue, Tang Xinran, Wen Xin, Yang Xiaojing, Sun Ying, Zeng Jing, Yun Jingping, Liu Na, Ma Jun
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
Department of Pathology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China.
Oncotarget. 2015 May 30;6(15):13309-19. doi: 10.18632/oncotarget.3751.
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.
本研究评估了间质-上皮转化因子(MET)蛋白过表达和基因扩增在局部区域晚期鼻咽癌(NPC)中的发生率及预后价值。对376例连续的局部区域晚期NPC患者的标本进行免疫组织化学分析MET蛋白表达,并采用荧光原位杂交评估MET扩增状态。总共139/376(37.0%)例患者存在MET蛋白过表达;其中,7/139(5.0%)例存在MET扩增。MET过表达与局部区域复发(P = 0.009)、远处转移(P = 0.006)及死亡(P < 0.001)显著相关;MET扩增与死亡(P = 0.021)显著相关。观察到MET拷贝数状态与MET蛋白表达之间呈正相关(r = 0.629,P < 0.001)。多因素分析表明,MET过表达是总生存(OS;风险比[HR],1.99;95%置信区间[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,且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。总之,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生物标志物。