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通过生物信息学分析和临床验证发现血浆信使核糖核酸作为胃癌的新型生物标志物

Discovery of plasma messenger RNA as novel biomarker for gastric cancer identified through bioinformatics analysis and clinical validation.

作者信息

Cao Wei, Zhou Dan, Tang Weiwei, An Hanxiang, Zhang Yun

机构信息

Department of Medical Oncology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.

Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Provincial Key Laboratory of Nanomaterials, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, China.

出版信息

PeerJ. 2019 Jun 18;7:e7025. doi: 10.7717/peerj.7025. eCollection 2019.

Abstract

BACKGROUND

Gastric cancer (GC) is the third leading cause of cancer-related death worldwide, partially due to the lack of effective screening strategies. Thus, there is a stringent need for non-invasive biomarkers to improve patient diagnostic efficiency in GC.

METHODS

This study initially filtered messenger RNAs (mRNAs) as prospective biomarkers through bioinformatics analysis. Clinical validation was conducted using circulating mRNA in plasma from patients with GC. Relationships between expression levels of target genes and clinicopathological characteristics were calculated. Then, associations of these selected biomarkers with overall survival (OS) were analyzed using the Kaplan-Meier plotter online tool.

RESULTS

Based on a comprehensive analysis of transcriptional expression profiles across 5 microarrays, top 3 over- and underexpressed mRNAs in GC were generated. Compared with normal controls, expression levels of (, and were significantly upregulated in GC plasmas. Receiver-operating characteristic (ROC) curves on the diagnostic efficacy of plasma , and mRNAs in GC showed that the area under the ROC (AUC) was 0.720, 0.698 and 0.833, respectively. Combined, these three biomarkers showed an elevated AUC of 0.907. Interestingly, the higher level was significantly correlated with lymph node metastasis and poor prognosis in GC patients. High level of mRNA expression was correlated with advanced age, poor differentiation, lower OS, and was also associated with poor OS in GC patients.

CONCLUSION

Our results suggested that circulating , and mRNAs could be putative noninvasive biomarkers for GC diagnosis and prognosis.

摘要

背景

胃癌(GC)是全球癌症相关死亡的第三大主要原因,部分原因是缺乏有效的筛查策略。因此,迫切需要非侵入性生物标志物来提高胃癌患者的诊断效率。

方法

本研究最初通过生物信息学分析筛选信使核糖核酸(mRNA)作为潜在生物标志物。使用胃癌患者血浆中的循环mRNA进行临床验证。计算靶基因表达水平与临床病理特征之间的关系。然后,使用Kaplan-Meier绘图仪在线工具分析这些选定生物标志物与总生存期(OS)的关联。

结果

基于对5个微阵列转录表达谱的综合分析,得出了胃癌中表达上调和下调的前3种mRNA。与正常对照相比,胃癌血浆中 、 和 的表达水平显著上调。血浆 、 和 mRNA对胃癌诊断效能的受试者工作特征(ROC)曲线显示,ROC曲线下面积(AUC)分别为0.720、0.698和0.833。这三种生物标志物联合使用时,AUC升高至0.907。有趣的是,较高的 水平与胃癌患者的淋巴结转移和不良预后显著相关。高水平的 mRNA表达与高龄、低分化、较低的总生存期相关,并且也与胃癌患者的不良总生存期相关。

结论

我们的结果表明,循环 、 和 mRNA可能是用于胃癌诊断和预后的非侵入性生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a7d/6587939/b68708f7d4ff/peerj-07-7025-g001.jpg

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