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[早期食管鳞状细胞癌中转移相关微小RNA的表达谱分析]

[Expression profiling of metastasis-related microRNAs in early esophageal squamous cell carcinoma].

作者信息

Lu Jun, Xue Liyan, Jin Mulan, Lyu Ning

机构信息

Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.

Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing 100021, China. E-mail:

出版信息

Zhonghua Bing Li Xue Za Zhi. 2014 May;43(5):313-7.

Abstract

OBJECTIVE

To study the difference of microRNA (miRNA) expression between two groups of early stage (pT1N0) esophageal squamous cell carcinoma (ESCC) patients who had different outcome and the prognostic significance of different miRNA in metastatic of early ESCC, and to identify useful prognostic markers in the selection of appropriate treatment for early ESCC patients.

METHODS

TaqMan human miRNA arrays and bioinformatics were used to detect and analyze the expression profiles of miRNAs in the two groups, and RT-PCR was used to verify the differences in miRNA expression.

RESULTS

The miRNA arrays revealed a total of 41 markedly changed miRNAs in the survival group compared with the death group. Bioinformatics analysis, prediction and significant function analyses of targeted genes and pathway analysis identified that miR-27a, miR-143 and miR-886-5p levels were increased or decreased by seven-folds or more. The enriched target genes were GRB2, SOS1, MAPK1, EGFR, CBL, SPRY2, RPS6KA5, IGF1R, NGFR, MAPK14 and CREB1. These genes were significantly related to the following signaling pathways, i.e.Sprouty regulation of tyrosine kinase signals pathway, Erk1/Erk2 Mapk signaling pathway and transcription factor CREB and its extracellular signals.

CONCLUSIONS

miR-27a, miR-886-5p, and miR-143 may be potential prognostic markers of metastasis for early ESCC. The detection of these miRNAs plays a directive role for the treatment options of early ESCC. The regulation of targeted genes and mechanism remain to be further studied.

摘要

目的

研究两组预后不同的早期(pT1N0)食管鳞状细胞癌(ESCC)患者之间微小RNA(miRNA)表达的差异,以及不同miRNA在早期ESCC转移中的预后意义,并在为早期ESCC患者选择合适治疗方法时确定有用的预后标志物。

方法

采用TaqMan人类miRNA芯片和生物信息学方法检测和分析两组中miRNA的表达谱,并采用逆转录-聚合酶链反应(RT-PCR)验证miRNA表达的差异。

结果

与死亡组相比,miRNA芯片显示生存组共有41种miRNA有明显变化。通过生物信息学分析、靶向基因预测和显著功能分析以及通路分析确定,miR-27a、miR-143和miR-886-5p的水平升高或降低了7倍或更多。富集的靶基因有GRB2、SOS1、MAPK1、EGFR、CBL、SPRY2、RPS6KA5、IGF1R、NGFR、MAPK14和CREB1。这些基因与以下信号通路显著相关,即酪氨酸激酶信号通路的Sprouty调节、Erk1/Erk2丝裂原活化蛋白激酶(Mapk)信号通路以及转录因子CREB及其细胞外信号。

结论

miR-27a、miR-886-5p和miR-143可能是早期ESCC转移的潜在预后标志物。检测这些miRNA对早期ESCC的治疗选择具有指导作用。其靶向基因的调控及机制仍有待进一步研究。

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