WFDC1基因在肝癌中的表达及其诊断和预后价值

doi:10.3969/j.issn.1004-616x.2018.04.009

癌变·畸变·突变 ›› 2018, Vol. 30 ›› Issue (4): 291-296.doi: 10.3969/j.issn.1004-616x.2018.04.009

WFDC1基因在肝癌中的表达及其诊断和预后价值

赵吉^1,2, 刘文斌², 陈洪强², 刘晋祎², 杨惠芳¹, 曹佳²

1. 宁夏医科大学公共卫生与管理学院, 宁夏银川 750004;
2. 陆军军医大学军事预防医学院毒理学研究所, 重庆 400038

收稿日期:2017-09-22 修回日期:2018-04-27 出版日期:2018-07-30 发布日期:2018-07-30
通讯作者: 曹佳,E-mail:caojia1962@126.com;杨惠芳,E-mail:joyceyhf@163.com E-mail:caojia1962@126.com;joyceyhf@163.com
作者简介:赵吉,E-mail:285705849@qq.com
基金资助:
国家自然科学基金（81230064）

Expression of the WFDC1 gene in hepatocellular carcinoma tissues and cell lines and their prognostic values

ZHAO Ji^1,2, LIU Wenbin², CHEN Hongqiang², LIU Jinyi², YANG Huifang¹, CAO Jia²

1. College of Public Health and Management, Ningxia Medical University, Yinchuan 750004, Ningxia;
2. Institute of Toxicology, College of Preventive Medicine, Army Medical University, Chongqing 400038, China

Received:2017-09-22 Revised:2018-04-27 Online:2018-07-30 Published:2018-07-30

摘要/Abstract

摘要： 目的：研究WFDC1基因在肝癌组织和细胞中的表达变化，探讨其与肝癌临床病理指标及生存预后之间的关系，为肝癌的诊断以及预后判断提供参考依据。方法：采用qPCR法分别检测肝癌患者的肿瘤组织和癌旁组织、MC-LR诱导的人肝细胞L02恶性转化细胞和肝癌细胞株SMMC-7721、HepG2、Hep3B、Huh-7中WFDC1 mRNA的表达水平。基于TCGA数据库，分析WFDC1基因在肝癌患者肿瘤组织（331例）和癌旁组织（50例）中的表达及其与临床病理指标和生存预后的关系。结果：qPCR检测结果表明，与癌旁组织比较，WFDC1 mRNA在肝癌组织、MC-LR诱导的L02恶性转化细胞以及肝癌细胞中的表达均显著下调（P < 0.05）。TCGA数据库中WFDC1 mRNA表达分析也表明，肝癌组织的表达显著低于癌旁组织（P < 0.01），且WFDC1 mRNA的表达下调与肿瘤分级和临床分期高度相关（P < 0.05）。Kaplan-Meier分析表明，WFDC1 mRNA高表达患者生存时间高于低表达患者（Log-rank=4.80，P < 0.05）。ROC曲线分析结果表明，WFDC1 mRNA是一个特异度和灵敏度较好的肝癌诊断指标（AUC=0.829）。结论：WFDC1基因可能是一个抑癌基因，检测该基因的表达水平对肝癌患者的诊断和预后判断具有参考价值。

关键词: WFDC1基因, 肝癌, 基因表达, 生存预后

Abstract: OBJECTIVE: To investigate expression of the WFDC1 gene in hepatocellular tissues and cell lines and their clinicopathological values. METHODS: Expression of WFDC1 mRNA was detected using qPCR in tumor and adjacent tissues from patients with liver cancer,as well as in MC-LR-induced L02 malignantly transformed cells and in hepatocellular carcinoma cell lines. Expression in 331 cases of tumor tissues and 50 cases of adjacent tissues was analyzed based on the TCGA database. The relationship between expression of WFDC1 and survival and clinicopathological parameters was also studied. RESULTS: Results from the qPCR analyses show that expression of WFDC1 was significantly down-regulated in hepatocellular carcinoma tissues,MC-LR-induced L02 malignantly transformed cells and hepatocellular carcinoma cells (P < 0.05). The expression of WFDC1 in paracancerous tissues was significantly higher than that in tumor tissues in TCGA database (P < 0.01). Kaplan-Meier analysis show that patients with high expression of WFDC1 had longer survival time than those with low expression (Log-rank=4.80,P < 0.05). The results of ROC curve analysis show that the expression of WFDC1 was a specific and sensitive indicator of liver cancer (AUC=0.829). CONCLUSION: WFDC1 may be a tumor suppressor gene which can possibly provide reference value for diagnosis and survival prognosis of patients with liver cancer.

Key words: WFDC1 gene, hepatocellular carcinoma, gene expression, prognosis

中图分类号:

R730.2

赵吉, 刘文斌, 陈洪强, 刘晋祎, 杨惠芳, 曹佳. WFDC1基因在肝癌中的表达及其诊断和预后价值[J]. 癌变·畸变·突变, 2018, 30(4): 291-296.

ZHAO Ji, LIU Wenbin, CHEN Hongqiang, LIU Jinyi, YANG Huifang, CAO Jia. Expression of the WFDC1 gene in hepatocellular carcinoma tissues and cell lines and their prognostic values[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2018, 30(4): 291-296.

参考文献

[1] SIEGEL R L,MILLER K D,JEMAL A. Cancer statistics,2016[J]. CA Cancer J Clin,2016,66(1):7-30.
[2] 梁宾勇,黄志勇,陈孝平. 精准医学背景下肝癌的治疗策略[J]. 临床外科杂志,2017,25(1):5-7.
[3] 黄乾荣,张玲. 原发性肝癌治疗研究新进展[J]. 实用医学杂志,2016,32(14):2275-2278.
[4] 方淼,郑文杰,姚敏,等. 肝癌特异诊断新标志物发现及其临床应用前景[J]. 世界华人消化杂志,2017(10):865-873.
[5] CHEN H Q,ZHAO J,LI Y,et al. Gene expression network regulated by DNA methylation and microRNA during microcystin-leucine arginine induced malignant transformation in human hepatocyte L02 cells[J]. Toxicol Lett,2018,289:42-53.
[6] RESSLER S J,DANG T D,WU S M,et al. WFDC1 is a key modulator of inflammatory and wound repair responses[J]. Am J Pathol,2014,184(11):2951-2964.
[7] HICKMAN O J,SMITH R A,DASGUPTA P,et al. Expression of two WFDC1/ps20 isoforms in prostate stromal cells induces paracrine apoptosis through regulation of PTGS2/COX-2[J]. Br J Cancer,2016,114(11):1235-1242.
[8] LIU S,HOWELL P,REN S,et al. Expression and functional analysis of the WAP four disulfide core domain 1 gene in human melanoma[J]. Clin Exp Metastasis,2009,26(7):739-749.
[9] MADAR,BROSH R,BUGANIM Y,et al. Modulated expression of WFDC1 during carcinogenesis and cellular senescence[J]. Carcinogenesis.,2009,30(1):20-27.
[10] 黄永胜,刘文斌,韩飞,等. 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.
[11] RESSLER S J,ROWLEY D R. The WFDC1 gene:role in wound response and tissue homoeostasis[J]. Biochem Soc Trans,2011,39(5):1455-1459.
[12] LARSEN M,RESSLER S J,GERDES M J,et al. The WFDC1 gene encoding ps20 localizes to 16q24,a region of LOH in multiple cancers[J]. Mamm Genome,2000,11(9):767-773.
[13] WATSON J E,KAMKAR S,JAMES K,et al. Molecular analysis of WFDC1/ps20 gene in prostate cancer[J]. Prostate,2004,61(2):192-199.
[14] KUROSE K,GILLEY K,MATSUMOTO S,et al. Frequent somatic mutations in PTEN and TP53 are mutually exclusive in the stroma of breast carcinomas[J]. Nat Genet,2002,32(3):355-357.
[15] GRAMANTIERI L,TRERE D,PESSION A,et al. Allelic imbalance on 16q in small,unifocal hepatocellular carcinoma:correlation with HBV and HCV infections and cellular proliferation rate[J]. Dig Dis Sci,2000,45(2):306-311.
[16] RIKER A I,ENKEMANN S A,FODSTAD O,et al. The gene expression profiles of primary and metastatic melanoma yields a transition point of tumor progression and metastasis[J]. BMC Med Genomics,2008,1:13.
[17] ALVAREZ R,READING J,KING D F,et al. WFDC1/ps20 is a novel innate immunomodulatory signature protein of human immunodeficiency virus (HIV)-permissive CD4+ CD45RO+ memory T cells that promotes infection by upregulating CD54 integrin expression and is elevated in HIV type 1 infection[J]. J Virol,2008,82(1):471-486.
[18] ALVAREZ R A,THORBORN G,READING J L,et al. WFDC1 expression identifies memory CD4 T-lymphocytes rendered vulnerable to cell-cell HIV-1 transfer by promoting intercellular adhesive junctions[J]. Retrovirology,2011,8:29.

WFDC1基因在肝癌中的表达及其诊断和预后价值

Expression of the WFDC1 gene in hepatocellular carcinoma tissues and cell lines and their prognostic values

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