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细胞周期蛋白在胃癌中的临床意义及生物学作用

Clinical significance and biological roles of cyclins in gastric cancer.

作者信息

Zhang Hai-Ping, Li Shu-Yu, Wang Jian-Ping, Lin Jun

机构信息

Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan City, Hubei Province 430071, China,

Department of Gastroenterology, Zhongshan Hospital of Hubei Province, Wuhan City, Hubei Province 430071, China.

出版信息

Onco Targets Ther. 2018 Oct 9;11:6673-6685. doi: 10.2147/OTT.S171716. eCollection 2018.

Abstract

BACKGROUND AND AIM

Cyclins have been reported to be overexpressed with poor prognosis in several human cancers. However, limited numbers of studies evaluated the expressions and prognostic roles of cyclins in gastric cancer (GC). We aim to evaluate the expressions and prognostic roles of cyclins. Also, further efforts were made to explore biological function of the differentially expressed cyclins.

METHODS

Cyclins expressions were analyzed by Oncomine and The Cancer Genome Atlas datasets, and the prognostic roles of cyclins in GC patients were investigated by the Kaplan-Meier Plotter database. Then, a comprehensive PubMed literature search was performed to identify expression and prognosis of cyclins in GC. Biological functions of the differentially expressed cyclins were explored through Enrich R platform, and KEGG and transcription factor were analyzed.

RESULTS

The expression levels of CCNA2 (cyclin A2), CCNB1 (cyclin B1), CCNB2 (cyclin B2), and CCNE1 (cyclin E1) mRNAs were identified to be significantly higher in GC tissues than in normal tissues in both Oncomine and The Cancer Genome Atlas datasets. High expressions of CCNA2, CCNB1, and CCNB2 mRNAs were identified to be related with poor overall survival in Kaplan-Meier Plotter dataset. Evidence from clinical studies showed that CCNB1 was related with overall survival in GC patients. Cyclins were associated with several biological pathways, including cell cycle, p53 signaling pathway, FoxO signaling pathway, viral carcinogenesis, and AMPK signaling pathway. Enrichment analysis also showed that cyclins interacted with some certain transcription factors, such as FOXM1, SIN3A, NFYA, and E2F4.

CONCLUSION

Based on our results, high expressions of cyclins were related with poor prognosis in GC patients. The above information might be useful for better understanding the clinical and biological roles of cyclins mRNA and guiding individualized treatments for GC patients.

摘要

背景与目的

据报道,细胞周期蛋白在多种人类癌症中过表达且预后不良。然而,评估细胞周期蛋白在胃癌(GC)中表达及预后作用的研究数量有限。我们旨在评估细胞周期蛋白的表达及预后作用。此外,还进一步努力探索差异表达的细胞周期蛋白的生物学功能。

方法

通过Oncomine和癌症基因组图谱数据集分析细胞周期蛋白的表达,并通过Kaplan-Meier Plotter数据库研究细胞周期蛋白在GC患者中的预后作用。然后,进行全面的PubMed文献检索以确定细胞周期蛋白在GC中的表达和预后。通过Enrich R平台探索差异表达的细胞周期蛋白的生物学功能,并分析KEGG和转录因子。

结果

在Oncomine和癌症基因组图谱数据集中,均发现GC组织中CCNA2(细胞周期蛋白A2)、CCNB1(细胞周期蛋白B1)、CCNB2(细胞周期蛋白B2)和CCNE1(细胞周期蛋白E1)mRNA的表达水平显著高于正常组织。在Kaplan-Meier Plotter数据集中,CCNA2、CCNB1和CCNB2 mRNA的高表达与总生存期较差相关。临床研究证据表明,CCNB1与GC患者的总生存期相关。细胞周期蛋白与多种生物学途径相关,包括细胞周期、p53信号通路、FoxO信号通路、病毒致癌作用和AMPK信号通路。富集分析还表明,细胞周期蛋白与某些转录因子相互作用,如FOXM1、SIN3A、NFYA和E2F4。

结论

基于我们的结果,细胞周期蛋白的高表达与GC患者的预后不良相关。上述信息可能有助于更好地理解细胞周期蛋白mRNA的临床和生物学作用,并指导GC患者的个体化治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9721/6186297/c332bf4e316b/ott-11-6673Fig1.jpg

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