MUC15和PI3K/Akt表达与胃癌临床病理特征及预后的相关性研究

2016-03-31韩志伟戎瑞洲孔鹏洲程彩霞张燕燕董金垚李曙晶郭建昇

中国肿瘤临床 2016年2期

韩志伟戎瑞洲孔鹏洲程彩霞张燕燕董金垚李曙晶郭建昇

韩志伟①戎瑞洲①孔鹏洲②②程彩霞④张燕燕①董金垚①李曙晶①郭建昇①

摘要目的：探讨MUC15和PI3K/Akt的表达与胃癌临床病理特征和预后的关系。方法：采用组织芯片和免疫组织化学法检测144例胃癌组织及对应癌旁组织中MUC15、Akt的表达。结果：MUC15在胃癌中阳性表达率为79.8%，高于癌旁组织中的阳性表达率22.2%（P<0.01）；Akt在胃癌中阳性表达率为80.6%，高于癌旁组织的阳性表达率16.7%（P<0.01）。MUC15和Akt表达均与胃癌分化程度、浸润深度、有无淋巴结转移和TNM分期相关（P<0.05）；且胃癌组织中MUC15表达和Akt表达呈正相关（P=0.001）。单因素生存分析显示，MUC15和Akt高表达均与生存时间呈负相关（P<0.05）。Cox多元回归分析提示，MUC15和Akt同时阳性的胃癌患者预后更差（HR=3.115，P<0.05）。结论：MUC15可能通过PI3K/Akt细胞信号转导通路参与胃癌的发生、发展、浸润转移，MUC15结合Akt是胃癌预后强有力的预测因子。

关键词胃癌免疫组织化学MUC15 PI3K/Akt预后

Expression of MUC15 and PI3K/Akt in gastric carcinoma and its association with clinicopathological characteristics and prognosis

Zhiwei HAN1, Ruizhou RONG1, Pengzhou KONG2,3, Caixia CHENG4, Yanyan ZHANG1, Jinyao DONG1, Shujing LI1, Jiansheng GUO1
Correspondence to: Jiansheng GUO; E-mail: jianshengguo@sina.com
1Department of General Surgery, the First Hospital, Shanxi Medical University, Taiyuan 030001, China;2Translational Medicine Research Center, Shanxi Medical University, Taiyuan 030001, China;3Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China;4Department of Pathology, the First Hospital, Shanxi Medical University, Taiyuan 030001, China

Abstract Objective: To analyze the expression of MUC15 and PI3K/Akt in gastric carcinoma and its association with clinicopathological characteristics and prognosis.Methods: The expression of MUC15 and Akt was detected in 144 cases of gastric carcinoma tissues and corresponding para-carcinoma tissues by tissue microarray and immunohistochemistry.Results: The positive expression rate of MUC15 in gastric carcinoma was 79.8%, higher than that of para-carcinoma tissues（22.2%, P<0.01）.The positive expression rate of Akt protein in gastric carcinoma was 80.6%, higher than that of para-carcinoma tissues（16.7%, P<0.01）.The expression of MUC15 and Akt was statistically associated with the grades of differentiation, invasion depth, lymphatic metastasis, TNM stage of tumor tissues（P< 0.05）, and the positive correlation between the two protein expression that appear in the gastric tumor tissue（P=0.001）.Univariate survival analysis showed that the over-expression of either MUC15 or Akt was inversely correlated with the survival time（P<0.05 and P<0.01, respectively）.Cox multiple regression analysis indicated that patients with over-expression of both MUC15 and Akt had the worst prognoses（HR=3.115, P<0.05）.Conclusion: MUC15 may be involved in the occurrence, development, invasion, and metastasis of gastric cancer through the PI3K/Akt cell signaling pathway, and the expression of MUC15 combined with Akt is a powerful predictor for the prognosis of gastric cancer.

Keywords:gastric carcinoma, immunohistochemistry, MUC15, PI3K/Akt, prognosis

在我国，胃癌发病率和死亡率分别居恶性肿瘤的第2位和第3位［1］，晚期胃癌患者5年生存率仅20%［2］。随着胃癌分子生物学研究的深入，胃癌的分子靶向治疗成为胃癌研究的重点与热点［3］。粘蛋白（mucin，MUC）家族成员MUC15可通过改变细胞间黏附、调控信号通路等途径在肿瘤的发生发展中起到极为重要的作用［4-5］。研究表明MUC15可调控PI3K/Akt信号通路的失活，抑制肝癌细胞迁移及侵袭的能力［6］。PI3K/Akt信号转导通路的失调在细胞凋亡、细胞侵袭与转移、细胞周期调节、肿瘤血管形成以及化疗耐药中发挥了重要的作用，是肿瘤靶向治疗的热点［7-8］。但是MUC15在胃癌中的表达和作用及其与PI3K/Akt在胃癌中的相关性研究鲜见报道。本研究利用组织芯片和免疫组织化学技术检测MUC15和PI3K/Akt在胃癌组织、癌旁组织的表达，分析MUC15 和PI3K/Akt信号通路表达与胃癌临床病理特征及胃癌患者术后预后的相关性，为发现新的胃癌预后指标和靶向治疗位点提供理论支持。