MAP4K4在胰腺癌中的表达及增殖功能的研究  

The expression of MAP4K4 in pancreatic cancer and its function of proliferation

作　　者：卢诚 涂敏 傅跃 陈秋阳 刘东方 时国东 苗毅 高文涛 Lu Cheng;Tu Min;Fu Yue;Chen Qiuyang;Liu Dongfang;Shi Guodong;Miao Yi;Gao Wentao(Pancreas Centre, the First Affiliated Hospital of NMU, Nanjing 210029, China)

机构地区：[1]南京医科大学第一附属医院胰腺中心,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2018年第6期721-727,共7页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金(81372657;81572381;81672449);江苏省自然科学基金(BK20151027);江苏高校优势学科建设工程资助(JX10231801);江苏省创新能力建设专项(BM2015004);江苏省医学重点学科(ZDXKA2016005)

摘　　要：目的:检测丝裂原激活蛋白激酶4(MAP4K4)在胰腺癌中的表达及意义,并研究其对胰腺癌细胞增殖功能的影响。方法:检索GEPIA和Oncomine数据库,分析MAP4K4在胰腺癌以及正常胰腺组织中的表达;检索GEPIA和Onco Lnc数据库,分析MAP4K4的表达量与胰腺癌患者生存期之间的关系。免疫组化检测MAP4K4在人胰腺癌及癌旁组织中的表达并分析其与胰腺癌患者临床病理参数的相关性以及生存分析。q RT-PCR和Western blot检测MAP4K4在人胰腺癌细胞株中的表达。慢病毒感染人胰腺癌细胞株CFPAC-1和MIA Pa Ca-2构建MAP4K4过表达及干扰细胞株,CCK-8和克隆形成实验研究其增殖能力变化。结果:GEPIA和Oncomine数据库显示MAP4K4在人胰腺癌中的表达显著高于正常胰腺组织(P<0.01)。GEPIA和On-co Lnc数据库表明胰腺癌中高表达MAP4K4组患者的总体和无病生存期显著低于低表达组患者(P<0.01)。免疫组化表明MAP4K4在人胰腺癌组织中的表达高于癌旁组织并与肿瘤大小、肿瘤分化相关(P<0.05),生存分析提示MAP4K4高表达的胰腺癌患者生存时间显著低于MAP4K4低表达的患者(P<0.05)。MAP4K4过表达及干扰胰腺癌细胞株构建成功,过表达后胰腺癌细胞株增殖能力明显增加而干扰后显著降低(P<0.05)。结论:MAP4K4在胰腺癌中表达增高并与预后负相关,且促进胰腺癌细胞增殖。Objective：To investigate the expression and significance of MAP4K4 in pancreatic cancer（PC）and study its effect onproliferation. Methods：GEPIA and Oncomine databases were retrieved to analyze the expression of MAP4K4 in pancreatic tumors andnormal pancreatic tissues;GEPIA and Onco Lnc databases were performed to assess the relationship between MAP4K4 level and thesurvival time for patients with PC. Immunohistochemistry was used to detect the expression of MAP4K4 in human pancreatic tumorsand adjacent normal tissues,then correlation and survival analysis were conducted to investigate the relationship between MAP4K4 level and clinicopathological parameters. q RT-PCR and Western blot were used to detect the expression of MAP4K4 in human PC celllines. Lentiviruses were used to infect CFPAC-1 and MIA Pa Ca-2 to construct the cell lines with MAP4K4 overexpression andinterfering,then CCK-8 and colony formation assay were conducted to study the influence of MAP4K4 on proliferation. Results：GEPIA and Oncomine databases showed that the expression of MAP4K4 was significantly higher in human pancreatic tumors than thatin normal pancreatic tissues（P 0.01）. GEPIA and Onco Lnc databases revealed that higher expression of MAP4K4 was significantlyassociated with poorer survival time of PC patients（P〈0.01）. Data derived from immunohistochemistry indicated that MAP4K4 levelwas higher in human pancreatic tumors than that in adjacent normal tissues and was correlated with tumor size and differentiation（P〈0.05）. Survival analysis showed that the survival time of patients with high level of MAP4K4 was significantly lower than that with lowlevel（P〈0.05）. Cell lines with MAP4K4 overexpression and interfering were successfully constructed. MAP4K4 overexpressionsignificantly promoted,whereas MAP4K4 knockdown inhibited PC cell proliferaton compared with controls respectively（P〈0.05）.Conclusion：The expression of MAP4K4 is up-regulated in PC and correlated with poor prognosis,and it plays an important r

关 键 词：MAP4K4 胰腺癌 表达 增殖 

分 类 号：R735.9[医药卫生—肿瘤]