胃腺癌组织c⁃MET EGFR和HER⁃2的表达与病理特
征及预后关系研究

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摘要目的探讨酪氨酸蛋白激酶Met（c⁃MET)、表皮生长因子受体（EGFR）和人表皮生长因子受体2（HER⁃2) 的表达与胃腺癌临床病理学特征及预后的相关性。方法选取2016年1月至2018年1月西安交通大学医学院附属三二〇一医院收治的87例行胃癌根治术的胃腺癌患者为研究对象，采用免疫组织化学法检测组织c⁃MET、EGFR和HER⁃2蛋白的表达，并分析其与Ki⁃67蛋白、临床病理特征的相关性，随访3年，根据c⁃MET、EGFR和HER⁃2蛋白表达情况分为阳性组与阴性组（c⁃MET阳性组37例，阴性组50 例；EGFR阳性组33例，阴性组54例；HER⁃2阳性组39例，阴性组48例），比较各组间无复发生存率及总生存率，采用Cox比例风险回归模型（Cox回归）分析进行多因素生存分析。结果胃腺癌中，c⁃MET、EGFR和HER⁃2蛋白阳性率分别为42.53%、37.93%和 44.83%，高于癌旁正常组织，差异有统计学意义（P<0.05）。患者病理特征中，低分化程度、浸润深度（T3+T4 ）、TNM分期Ⅲ期、有淋巴结转移、有远处转移、有癌栓的胃腺癌患者的c-MET、EGFR和HER-2蛋白阳性率高于中高分化、浸润深度（T1+T2 ）、TNM分期Ⅰ、Ⅱ 期、无淋巴结转移、无远处转移、无癌栓患者，差异有统计学意义（P<0.05）。c⁃MET、EGFR和HER⁃2蛋白阳性表达与Ki⁃67蛋白阳性表达均呈正相关（r=0.319、0.338、0.374；均P<0.05）。随访3年，31例患者死亡，存活率为64.37%；31例患者复发，无复发生存率为 64.37%。c⁃MET、EGFR和HER⁃2阳性组中位生存时间分别为19.95、19.28和21.49个月，阴性组中位生存时间分别为33.84、33.10 和33.26个月。c⁃MET、EGFR和HER⁃2阳性组中位无复发生存时间分别为14.59、13.84和15.35个月，阴性组分别为27.83、27.37和 27.57个月。c⁃MET、EGFR和HER⁃2阳性组无复发生存率及总生存率低于表达阴性组（P<0.05）。 EGFR蛋白阳性是影响胃腺癌总生存期的独立预后因素（RR=4.278, 95%CI=2.099~8.713, P<0.05）。结论胃腺癌c⁃MET、EGFR和HER⁃2蛋白表达与分化程度、浸润深度、TNM分期、淋巴结转移、远处转移及癌栓有关，c⁃MET、EGFR和HER⁃2蛋白表达阳性患者复发率更高，无复发生存率及总生存率低，且预后差。EGFR蛋白阳性是影响患者总生存期的独立预后因素。

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	年瑞
	李万军
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关键词 ：胃腺癌, 酪氨酸蛋白激酶Met, 表皮生长因子受体, 人表皮生长因子受体2

Abstract：Objective To investigate the expression of c⁃MET, EGFR and HER⁃2 in gastric adenocarcinoma and their correlation with clinicopathological features and prognosis. Method From January 2016 to January 2018, 87 patients with gastric adenocarcinoma who underwent radical gastrectomy from the 3201 Hospital Affiliated toMedical College of Xi'an Jiaotong University were selected as the research objects.The expressions of c⁃MET,EGFR and HER⁃2 proteins in tissues were detected by immunohistochemical method, and their correlations with Ki⁃67 protein and clinicopathological features were analyzed.They were dividedinto positive group and negative group (37 casesin c⁃MET positive group and 50 cases in c⁃MET negative group). There were 33 cases in EGFR positive group and 54 cases in EGFR negative group. There were 39 cases in HER⁃2 positive group and 48 cases in HER⁃2 negative group.The recurrence free survival rate and overall survival rate were compared among the groups. ResultIn the pathological characteristics of the patients, the difference in the degree of differentiation,TNM stage, lymph node metastasis, distant metastasis, and tumor thrombus positive rate of c⁃MET, EGFR and HER⁃2 protein was statistically significant(P<0.05). The positive expression of c⁃MET, EGFR and HER⁃2 protein was positively correlated with the positive expression of Ki⁃67 protein (r=0.319, 0.338, 0.374;P<0.05).After 3 years of follow⁃up, 31 patients died andthe survival rate was 64.37%; 31 patients relapsed, and the recurrence⁃free survival rate was 64.37%. The median survival time of c⁃MET, EGFR and HER⁃2 positive group were 19.95, 19.28 and 21.49months, andthe median survivaltime of negative group were 33.84, 33.10 and 33.26months,respectively.The median recurrence⁃free survival time of c⁃MET, EGFR and HER⁃2 positive group were 14.59, 13.84 and 15.35months, and the negative group were 27.83, 27.37 and 27.57 months. The recurrence⁃free survival rate and overall survival rate of c⁃MET, EGFR and HER⁃2 positive group were lower than those of negative expression group (P<0.05). Positive EGFR protein is an independent prognostic factor affecting the overall survival of gastric adenocarcinoma (RR=4.278, 95%CI=2.099-8.713, P<0.05). Conclusion The expression of c⁃MET, EGFR and HER⁃2 protein in gastric adenocarcinoma was related to the degree of differentiation, depth of invasion,TNM stage, lymph node metastasis, distant metastasis and tumor thrombus. Patients with positive expression of c⁃MET, EGFR and HER⁃2 protein had higher recurrence rate, lower relapse free survival rate and overall survival rate, and worse prognosis. Positive EGFR protein is an independent prognostic factor that affects the overall survival of patients.

Key words： Gastric adenocarcinoma Cellular?mesenchymal to epithelial transition factor Epidermal growth factor receptor; Human epidermal growth factor receptor 2

收稿日期: 2021-08-11

通讯作者: 年瑞，电子邮箱：ccnr123@163.com

引用本文:

年瑞，李万军，李维华. 胃腺癌组织c⁃MET EGFR和HER⁃2的表达与病理特征及预后关系研究[J]. 肿瘤代谢与营养电子杂志, 2022, 9(1): 61-65.
Nian Rui，Li Wanjun，Li Weihua. Expression of c‑MET, EGFR and HER‑2 in gastric adenocarcinoma and their correlation with clinicopathological features and prognosis. Electron J Metab Nutr Cancer, 2022, 9(1): 61-65.