Reduced expression of Dicer1 is associated with poor prognosis in patients with nasopharyngeal carcinoma
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摘要: 目的:Dicer1在RNA干扰的起始阶段起着重要作用,本研究旨在评估Dicer1在鼻咽癌组织中的表达及预后价值。方法:采用免疫组织化学染色法检测276例鼻咽癌活检标本的Dicer1蛋白表达,利用定量RT-PCR法分析56例鼻咽癌活检标本和11例鼻咽炎组织中Dicer1 mRNA水平,采用Cox回归分析确定独立预后因素,建立预后评分模型进行生存预测。结果:Dicer1的mRNA和蛋白在鼻咽癌组织中表达水平均明显偏低,Dicer1的mRNA表达水平与蛋白表达水平呈正相关。Dicer1的低表达与鼻咽癌患者远处转移的发生(P<0.01)以及患者死亡率(P<0.05)显著相关。Dicer1低表达与鼻咽癌患者的总体生存期(HR=2.32,95% CI:1.30~4.14,P<0.01)和无远处转移生存率(HR=2.56,95% CI:1.39~4.74,P<0.01)亦显著相关。此外,多变量分析显示Dicer1低表达和TNM分期是鼻咽癌患者总体生存期和无远处转移生存率的独立预后因素。Dicer1表达和TNM分期相结合的预后评分模型比Dicer1表达单独模型或TNM分期单独模型拥有更好的预后价值(P<0.05)。结论:Dicer1 mRNA和蛋白表达水平在鼻咽癌组织中均明显偏低,Dicer1的低表达可能是鼻咽癌患者新的预后标志物。Abstract: Objective: Dicer1 plays an important role in generation of microRNA, the purpose of this study was to evaluate Dicer11 expression and its prognostic value in nasopharyngeal carcinoma (NPC). Method: The protein expression of Dicer1 was examined by immunohistochemistry in 276 NPC specimens, and the mRNA levels of Dicer1 were analyzed by qRT-PCR in 56 NPC and 11 nasopharyngitis tissues. Cox regression analysis was used to identify independent prognostic factors, and a prognostic score model was constructed for survival prediction. Result: Expression of Dicer1 was downregulated in NPC tissues at both the mRNA and the protein levels, and there was a notable positive correlation between the expression levels of Dicer1 mRNA and protein. Low Dicer1 expression was positively correlated with distant metastasis (P<0.01) and death (P<0.05). In addition, low expression of Dicer1 was significantly associated with poorer overall survival (HR=2.32, 95%CI: 1.30~4.14, P<0.01) and poorer distant metastasis-free survival (HR=2.56, 95%CI: 1.39~4.74, P<0.01). Furthermore, multivariate analysis showed that low expression of Dicer1 and tumor-node-metastasis (TNM) stage were independent prognostic indicators for NPC patients. A prognostic score model combining the Dicer1 expression and TNM stage had a better prognostic value than the TNM stage alone model or Dicer1 expression alone model (P<0.05). Conclusion: Dicer1 was downregulated in NPC tissues at both the mRNA and the protein levels, and low expression of Dicer1 could be served as novel prognostic biomarker for NPC patients.
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Key words:
- dicer1 /
- reduced expression /
- nasopharyngeal carcinoma /
- prognosis /
- biomarker
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[1] EDGE S B, COMPTON C C. The American Joint Committee on Cancer:the 7th edition of the AJCC cancer staging manual and the future of TNM[J]. Ann Surg Oncol, 2010,17:1471-1474.
[2] MAO Y P,XIE F Y,LIU L Z,et al. Re-evaluation of 6th edition of AJCC staging system for nasopharyngeal carcinoma and proposed improvement based on magnetic resonance imaging[J]. Int J Radiat Oncol Biol Phys,2009,73:1326-1334.
[3] TUREN S,OZYAR E,ALTUNDAG K,et al. Serum lactate dehydrogenase level is a prognostic factor in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy[J]. Cancer Invest,2007,25:315-321.
[4] LV X,XIANG Y Q,CAO S M,et al. Prospective validation of the prognostic value of elevated serum vascular endothelial growth factor in patients with nasopharyngeal carcinoma:more distant metastases and shorter overall survival after treatment[J]. Head Neck,2011,33:780-785.
[5] HAMMOND S M. Dicing and slicing:the core machinery of the RNA interference pathway[J]. FEBS Lett,2005,579:5822-5829.
[6] FAGGAD A,BUDCZIES J,TCHERNITSA O,et al. Prognostic significance of Dicer expression in ovarian cancer-link to global microRNA changes and oestrogen receptor expression[J]. J Pathol,2010,220:382-391.
[7] CHIOSEA S,JELEZCOVA E,CHANDRAN U,et al. Overexpression of Dicer in precursor lesions of lung adenocarcinoma[J]. Cancer Res,2007,67:2345-2350.
[8] SUGITO N,ISHIGURO H,KUWABARA Y,et al. RNASEN regulates cell proliferation and affects survival in esophageal cancer patients[J]. Clin Cancer Res,2006,12:7322-7328.
[9] CHIOSEA S,JELEZCOVA E,CHANDRAN U,et al. Up-regulation of dicer,a component of the MicroRNA machinery,in prostate adenocarcinoma[J]. Am J Pathol,2006,169:1812-1820.
[10] GRELIER G,VOIRIN N,AY A S,et al. Prognostic value of Dicer expression in human breast cancers and association with the mesenchymal phenotype[J]. B J Cancer,2009,101:673-683.
[11] ZIGHELBOIM I,REINHART A J,GAO F,et al. DICER1 expression and outcomes in endometrioid endometrial adenocarcinoma[J]. Cancer,2011,117:1446-1453.
[12] FABER C,HORST D,HLUBEK F,et al. Overexpression of Dicer predicts poor survival in colorectal cancer[J]. Eur J Cancer,2011,47:1414-1419.
[13] CHEN Y,LIU M Z,LIANG S B,et al. Preliminary results of a prospective randomized trial comparing concurrent chemoradiotherapy plus adjuvant chemotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma in endemic regions of china[J]. Int J Radiat Oncol Biol Phys,2008,71:1356-1364.
[14] LI W,YU C P,XIA J,et al. Sphingosine kinase 1 is associated with gastric cancer progression and poor survival of patients[J]. Clin Cancer Res,2009,15:1393-1399.
[15] LIAO W T,WANG X,XU L H,et al. Centromere protein H is a novel prognostic marker for human nonsmall cell lung cancer progression and overall patient survival[J]. Cancer,2009,115:1507-1517.
[16] KÖRBLER T,GRSKOVIĆM,DOMINIS M,et al. A simple method for RNA isolation from formalin-fixed and paraffin-embedded lymphatic tissues[J]. Exp Mol Pathol,2003,74:336-340.
[17] MARSHALL O J. PerlPrimer:cross-platform,graphical primer design for standard,bisulphite and real-time PCR[J]. Bioinformatics,2004,20:2471-2472.
[18] YANG H I,YUEN M F,CHAN H L Y,et al. Risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B):development and validation of a predictive score[J]. Lancet Oncol,2011,12:568-574.
[19] 马兰,张基昌,崔燕,等. MicroRNAs与冠心病发生发展关系的研究进展[J]. 中国实验诊断学,2013,17(7):1354-1357.
[20] 赵延明,张媛,张罗. MicroRNA在过敏性疾病中的研究进展[J]. 中国耳鼻咽喉头颈外科,2012,18(12):646-649.
[21] 罗丹丹,罗玉萍,彭娟,等. miRNA. 9基因家族进化分析及其靶基因预测[J]. 中国细胞生物学学报,2011,33(5):510-519.
[22] 杨静. 沉默Dicer基因对人舌鳞癌细胞株Tca-8113生物学行为的影响[D]. 南方医科大学,2013.
[23] 闫兆伟,朱海涛,董琼珠,等. MicroRNA生物合成相关基因在肝癌中的表达及其意义[J]. 国际消化病杂志,2013,33(3):193-196.
[24] 孙志华,李振宇,陈叶珊,等. 局部晚期鼻咽癌放疗同步PF方案或顺铂单药的临床对照研究[J]. 临床肿瘤学杂志,2012,17(3):229-232.
[25] 杨光耀,杨康,温松奇,等. 核酸内切酶在肝门部胆管癌组织和细胞株中的表达和临床意义[J]. 中华肝胆外科杂志,2012,18(10):753-757.
[26] 龚唯,周菊英,吴琼,等. MRI成像对鼻咽癌的分期,诊断及治疗优势的探讨[J]. 肿瘤防治研究,2012,39(4):455-459.
[27] 季佳文,周怀君. 白藜芦醇对肿瘤中微小RNA的调节作用[J]. 国际肿瘤学杂志,2013,40(8):587-590.
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