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人类胃癌中代谢途径相关长链非编码RNA的全基因组表达谱分析及RP11-555H23.1作为一种新型诊断生物标志物的鉴定。

Global expression profiling of metabolic pathway-related lncRNAs in human gastric cancer and the identification of RP11-555H23.1 as a new diagnostic biomarker.

作者信息

Mo Xiaoyan, Wu Yuanyuan, Chen Li, Zhai Ming, Gao Zhengdong, Hu Kainan, Guo Junming

机构信息

Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China.

出版信息

J Clin Lab Anal. 2019 Feb;33(2):e22692. doi: 10.1002/jcla.22692. Epub 2018 Oct 15.

Abstract

BACKGROUND

Long noncoding RNAs (lncRNAs) have roles in regulating metabolism; however, the global expression profile of metabolic pathway-associated lncRNAs in gastric cancer is unknown. The purpose of our study was to examine metabolic pathway-related lncRNAs in gastric cancer and their possible diagnostic values.

METHODS

Differential expression patterns of metabolic pathway-related lncRNAs between gastric cancer and paired nontumor tissues were detected using metabolic pathway-associated lncRNA microarrays. The expression of RP11-555H23.1, one representative metabolic pathway-associated lncRNA, was validated using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). The associations between RP11-55H23.1 expression and the clinicopathological features of gastric cancer patients were analyzed. A receiver operating characteristic (ROC) curve was further established.

RESULTS

A total of 114 differentially expressed metabolic pathway-associated lncRNAs (fold change >2, P < 0.05) between cancer and nontumor tissues were found (GEO No. GSE96856). Among them, TUG1, RP11-555H23.1, RP1-257I20.13, UGP2, GCSHP3, and XLOC_000889 lncRNAs were downregulated more than sixfold in gastric cancer tissues. In contrast, RP11-605F14.2, TBC1D3P5, BC130595, LINC00475, RP11-19P22.6, BC080653, XLOC_004923, AFAP1-AS1, EPB49, and RP11-296I10.3 lncRNAs were upregulated more than sixfold in gastric cancer tissues. We further demonstrated that RP11-555H23.1 expression was significantly correlated with TNM stage (P = 0.038). The area under the ROC curve (AUC) was 0.65, and the specificity and sensitivity were 62% and 81%, respectively.

CONCLUSIONS

Metabolic pathway-associated lncRNAs play an important role in the occurrence of gastric cancer, and metabolic pathway-associated lncRNAs, such as RP11-555H23.1, may represent novel biomarkers of gastric cancer.

摘要

背景

长链非编码RNA(lncRNA)在调节代谢中发挥作用;然而,胃癌中代谢途径相关lncRNA的整体表达谱尚不清楚。我们研究的目的是检测胃癌中与代谢途径相关的lncRNA及其可能的诊断价值。

方法

使用代谢途径相关lncRNA微阵列检测胃癌组织与配对的非肿瘤组织之间代谢途径相关lncRNA的差异表达模式。使用定量实时逆转录-聚合酶链反应(qRT-PCR)验证一种代表性的代谢途径相关lncRNA即RP11-555H23.1的表达。分析RP11-55H23.1表达与胃癌患者临床病理特征之间的关联。进一步绘制受试者工作特征(ROC)曲线。

结果

在癌组织与非肿瘤组织之间共发现114种差异表达的代谢途径相关lncRNA(倍数变化>2,P<0.05)(GEO编号GSE96856)。其中,TUG1、RP11-555H23.1、RP1-257I20.13、UGP2、GCSHP3和XLOC_000889 lncRNA在胃癌组织中下调超过6倍。相反,RP11-605F14.2、TBC1D3P5、BC130595、LINC00475、RP11-19P22.6、BC080653、XLOC_004923、AFAP1-AS1、EPB49和RP11-296I10.3 lncRNA在胃癌组织中上调超过6倍。我们进一步证明RP11-555H23.1表达与TNM分期显著相关(P = 0.038)。ROC曲线下面积(AUC)为0.65,特异性和敏感性分别为62%和81%。

结论

代谢途径相关lncRNA在胃癌发生中起重要作用,并且代谢途径相关lncRNA,如RP11-555H23.1,可能代表胃癌的新型生物标志物。

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