长链非编码RNA HOTAIR在胃癌中的表达及意义
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摘要
目的探讨长链非编码RNA(lncRNA)HOX转录反义RNA(HOTAIR)在胃癌中的表达及意义。方法采用实时定量PCR法检测50例胃癌、配对癌旁正常组织及血浆标本中HOTAIR的水平,同时检测60例健康人血浆HOTAIR作为对照。比较胃癌和癌旁正常组织、胃癌患者和健康对照者血浆HOTAIR的表达水平,分析胃癌组织和血浆中HOTAIR表达水平的相关性。采用ROC曲线分析,评价血浆lncRNA HOTAIR诊断胃癌的灵敏度和特异度。结果与癌旁正常组织相比,胃癌组织中HOTAIR的表达增高(P<0.01);胃癌患者血浆中HOTAIR水平高于健康对照者(P<0.01),且与胃癌组织HOTAIR表达水平呈正相关(r2=0.60,P<0.01)。ROC曲线下面积为0.753(P<0.01),当最佳诊断界值设为1.4786时,血浆lncRNA HOTAIR诊断胃癌的灵敏度和特异度分别为58.3%和81.7%。结论血浆HOTAIR可作为新的胃癌诊断标志物。
Objective To study the expression and significance of long non-coding RNA HOX transcript antisense intergenic RNA(lncRNA HOTAIR)in gastric cancer.Methods The levels of HOTAIR in gastric cancer tissues,tumor-adjacent normal tissues and plasma from 50 patients with gastric cancer and those in plasma from 60 healthy people were detected by real-time quantitative PCR,respectively.The levels of HOTAIR in gastric cancer tissues and tumor-adjacent normal tissues were compared.So did in plasma from patients with gastric cancer and healthy people.The correlation of HOTAIR expression between gastric cancer tissues and plasma was analyzed.The sensitivity and specificity of plasma lncRNA HOTAIR in the diagnosis of gastric cancer were evaluated by ROC curve analysis.Results Compared with tumor-adjacent normal tissues,the level of HOTAIR was increased in gastric cancer tissues(P<0.01).Plasma level of HOTAIR was signifiantly higher in the patients with gastric cancer than that in healthy people(P<0.01),which was positively correlated with the level of HOTAIR in gastric cancer tissues(r2=0.60,P<0.01).The area under ROC curve was 0.753(P<0.01).Taking 1.4786 as the cutoff value,the sensitivity and specificity of plasma lncRNA HOTAIR in diagnosing gastric cancer were 58.3% and 81.7%,respectively.Conclusion HOTAIR may be taken as a potential biomarker for the diagnosis of gastric cancer.
Objective To study the expression and significance of long non-coding RNA HOX transcript antisense intergenic RNA(lncRNA HOTAIR)in gastric cancer.Methods The levels of HOTAIR in gastric cancer tissues,tumor-adjacent normal tissues and plasma from 50 patients with gastric cancer and those in plasma from 60 healthy people were detected by real-time quantitative PCR,respectively.The levels of HOTAIR in gastric cancer tissues and tumor-adjacent normal tissues were compared.So did in plasma from patients with gastric cancer and healthy people.The correlation of HOTAIR expression between gastric cancer tissues and plasma was analyzed.The sensitivity and specificity of plasma lncRNA HOTAIR in the diagnosis of gastric cancer were evaluated by ROC curve analysis.Results Compared with tumor-adjacent normal tissues,the level of HOTAIR was increased in gastric cancer tissues(P<0.01).Plasma level of HOTAIR was signifiantly higher in the patients with gastric cancer than that in healthy people(P<0.01),which was positively correlated with the level of HOTAIR in gastric cancer tissues(r2=0.60,P<0.01).The area under ROC curve was 0.753(P<0.01).Taking 1.4786 as the cutoff value,the sensitivity and specificity of plasma lncRNA HOTAIR in diagnosing gastric cancer were 58.3% and 81.7%,respectively.Conclusion HOTAIR may be taken as a potential biomarker for the diagnosis of gastric cancer.
引文
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[2]Gupta RA,Shah N,Wang KC,et al.Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis[J].Nature,2010,464(7291):1071-1076.
[3]Kogo R,Shimamura T,Mimori K,et al.Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers[J].Cancer Res,2011,71(20):6320-6326.
[4]Geng YJ,Xie SL,Li Q,et al.Large intervening non-coding RNA HOTAIR is associated with hepatocellular carcinoma progression[J].J Int Med Res,2011,39(6):2119-2128.
[5]Kim K,Jutooru I,Chadalapaka G,et al.HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer[J].Oncogene,2013,32(13):1616-1625.
[6]赫捷,赵平,陈万青.2011中国肿瘤登记年报[M].北京:军事医学科学出版社,2012:28-29.
[7]Lee NK,Lee JH,Park CH,et al.Long non-coding RNA HOTAIR promotes carcinogenesis and invasion of gastric cancer adenocarcinoma[J].Biochem Biophys Res Commun,2014,451(2):171-178.
[8]赵久达,徐兵河.长链非编码RNA与胃癌发生、发展、诊治及预后关系的研究进展[J].中华医学杂志,2015,95(2):153-155.
[9]Cao WJ,Wu HL,He BS,et al.Analysis of long non-coding RNA expression profiles in gastric cancer[J].World J Gastroenterol,2013,19(23):3658-3664.
[10]Zhou X,Yin C,Dang Y,et al.Identification of the long non-coding RNA H19in plasma as a novel biomarker for diagnosis of gastric cancer[J].Sci Rep,2015,5:11516.
[11]Liu XH,Sun M,Nie EQ,et al.Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER-2expression by sponging miR-331-3p in gastric cancer[J].Mol Cancer,2014,13:92.
[12]Zhang S,Chen S,Yang G,et al.Long noncoding RNA HOTAIR as an independent prognostic marker in cancer:a meta-analysis[J].PLoS One,2014,9(8):e105538.