肝癌组织中MPDZ基因拷贝数和表达变化及其诊断预后价值分析

doi:10.3969/j.issn.1004-616x.2017.03.001

癌变·畸变·突变 ›› 2017, Vol. 29 ›› Issue (3): 161-165.doi: 10.3969/j.issn.1004-616x.2017.03.001

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肝癌组织中MPDZ基因拷贝数和表达变化及其诊断预后价值分析

黄永胜, 刘文斌, 韩飞, 崔志鸿, 敖琳, 曹佳, 刘晋祎

第三军医大学军事预防医学院毒理研究所, 重庆 400038

收稿日期:2017-02-22 修回日期:2017-03-29 出版日期:2017-05-31 发布日期:2017-05-31
通讯作者: 刘晋祎,E-mail:jinyiliutmmu@163.com E-mail:jinyiliutmmu@163.com
作者简介:黄永胜,E-mail:yongshengh@126.com。
基金资助:
国家自然科学基金（81573179）

MPDZ copy number variations, expression and prognostic value in liver cancer

HUANG Yongsheng, LIU Wenbin, HAN Fei, CUI Zhihong, AO Lin, CAO Jia, LIU Jinyi

Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China

Received:2017-02-22 Revised:2017-03-29 Online:2017-05-31 Published:2017-05-31

摘要/Abstract

摘要： 目的：探讨MPDZ基因在肝癌组织中的拷贝数和表达变化情况，并评价其与临床病理指标之间的关系以及对肝癌诊断和预后判断的价值。方法：利用TCGA数据库分析MPDZ基因在299例肝癌组织中的拷贝数改变情况及其与表达的关系；同时分析TCGA数据中MPDZ基因在282例肝癌组织和50例癌旁组织中的表达及其与临床病理指标和生存预后的关系。结果：MPDZ基因在肝癌组织中存在明显的拷贝数变异，且拷贝数变异的主要类型为拷贝数缺失（31.44%）；同时MPDZ基因拷贝数缺失后MPDZ mRNA表达下调。MPDZ基因在肝癌组织中的表达显著低于癌旁组织，差异具有统计学意义（P < 0.05）。Kaplan-Meier分析显示，MPDZ基因低表达患者的生存时间短于高表达患者，差异具有统计学意义（Log-rank=12.48，P < 0.05）。受试者工作特征曲线（ROC）分析结果表明，MPDZ基因表达是一个灵敏度和特异度较好的肝癌诊断指标（AUC=0.86）。结论：MPDZ基因拷贝数缺失可能与肝癌的发生有关，MPDZ基因的表达对肝癌的诊断及生存预后判断具有参考价值。

关键词: MPDZ基因, 肝癌, 拷贝数变异, 表达

Abstract: OBJECTIVE:This study aimed to explore the copy number variations and expression of MPDZ and to evaluate their relationship with prognostic outcomes in liver cancer. METHODS:Copy number variations and expression of MPDZ were performed from TCGA database,and their relationships were analyzed. Expression of MPDZ in liver carcinoma (282 cases) and adjacent normal tissues (50 cases) were also performed,then the relationship between MPDZ expression and clinical pathological parameters,and its prognostic value were evaluated by statistical analysis. RESULTS:Copy number deletion (31.44%) was the most frequent copy number variations observed and it was associated with the expression of MPDZ. The expression was significantly lower than that in adjacent normal tissues (P < 0.05). Kaplan-Meier survival curves showed that patients with low MPDZ expression had significantly shorter overall survival time than those with higher MPDZ expression (Log-rank=12.48,P < 0.05). Receiver operating characteristic curve (ROC) showed that MPDZ gene expression was a sensitive and specific index of liver cancer diagnosis (AUC=0.86). CONCLUSION:MPDZ gene copy number deletion might be associated with the occurrence of liver cancer and the expression of MPDZ had some reference value for the diagnosis and prognosis of liver cancer.

Key words: MPDZgene, liver cancer, copy number variation, expression

中图分类号:

R730.2

黄永胜, 刘文斌, 韩飞, 崔志鸿, 敖琳, 曹佳, 刘晋祎. 肝癌组织中MPDZ基因拷贝数和表达变化及其诊断预后价值分析[J]. 癌变·畸变·突变, 2017, 29(3): 161-165.

HUANG Yongsheng, LIU Wenbin, HAN Fei, CUI Zhihong, AO Lin, CAO Jia, LIU Jinyi. MPDZ copy number variations, expression and prognostic value in liver cancer[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2017, 29(3): 161-165.

参考文献

[1] HASHEM B,SERAG E L. Epidemiology of viral hepatitis and hepatocellular carcinoma[J]. Gastroenterology,2012,142(6):1264-1273.
[2] SIEGEL R L,MILLER K D,JEMAL A. Cancer statistics, 2016[J]. CA:A Cancer J Clin,2016,66(1):7-30.
[3] ULLMER C,SCHMUCK K,FIGGE A,et al. Cloning and characterization of MUPP1,a novel PDZ domain protein[J]. FEBS Lett,1998,424(1/2):63-68.
[4] MARTIN T A,WATKINS G,MANSEL R E,et al. Loss of tight junction plaque molecules in breast cancer tissues is associated with a poor prognosis in patients with breast cancer[J]. Eur J Cancer,2004,40(18):2717-2725.
[5] SHEU J J C,LEE C H,KO J Y,et al. Chromosome 3p12.3-p14.2 and 3q26.2-q26.32 are genomic markers for prognosis of advanced nasopharyngeal carcinoma[J]. Cancer Epidem Biomark, 2009,18(10):2709-2716.
[6] 封杰,刘文斌,陈洪强,等. 肺癌患者MPDZ基因异常甲基化的研究[J]. 癌变·畸变·突变,2015,27(6):437-440.
[7] ULLMER C,SCHMUCK K,FIGGE A,et al. Cloning and characterization of MUPP1,a novel PDZ domain protein[J]. FEBS Lett,1998,424(1/2):63-68.
[8] ASSéMAT E,CROST E,PONSERRE M,et al. The multi-PDZ domain protein-1(MUPP-1) expression regulates cellular levels of the PALS-1/PATJ polarity complex[J]. Exp Cell Res,2013,319(17):2514-2525.
[9] FUJITA E,TANABE Y,IMHOF B A,et al. A complex of synaptic adhesion molecule CADM1,a molecule related to autism spectrum disorder,with MUPP1 in the cerebellum[J]. J Neurochem,2012,123(5):886-894.
[10] LANASPA M A,ALMEIDA N E,ANDRES-HERNANDO A,et al. The tight junction protein,MUPP1,is up-regulated by hypertonicity and is important in the osmotic stress response in kidney cells[J]. PNAS,2007,104:13672-13677.
[11] MILNER L C,SHIRLEY R L,KOZELL L B,et al. Novel MPDZ/MUPP1 transgenic and knockdown models confirm Mpdz's role in ethanol withdrawal and support its role in voluntary ethanol consumption[J]. Addict Biol,2015,20(1):143-147.
[12] AL-DOSARI M S,AL-OWAIN M,TULBAH M,et al. Mutation in MPDZ causes severe congenital hydrocephalus[J]. J Med Genet,2013,50(1):54-58.
[13] BALASUBRAMANIAN S,FAM S R,HALL R A. GABAB receptor association with the PDZ scaffold Mupp1 alters receptor stability and function[J]. J Biol Chem,2007,282(6):4162-4171.
[14] LEE S S,GLAUNSINGER B,MANTOVANI F,et al. Multi-PDZ domain protein MUPP1 is a cellular target for both adenovirus E4-ORF1 and high-risk papillomavirus type 18 E6 oncoproteins[J]. J Virol,2000,74(20):9680-9693.
[15] GUILLAUME J L,DAULAT A M,MAURICE P,et al. The PDZ protein mupp1 promotes Gi coupling and signaling of the Mt1 melatonin receptor[J]. J Biol Chem,2008,283(24):16762-16771.
[16] KATOH M. Function and cancer genomics of FAT family genes (review)[J]. Int J Oncol,2012,41(6):1913-1918.

肝癌组织中MPDZ基因拷贝数和表达变化及其诊断预后价值分析

MPDZ copy number variations, expression and prognostic value in liver cancer

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