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通过动态转录组分析鉴定出的miR-429是结直肠癌预后的一种新的候选生物标志物。

miR-429 identified by dynamic transcriptome analysis is a new candidate biomarker for colorectal cancer prognosis.

作者信息

Sun Yingnan, Shen Shourong, Tang Hailin, Xiang Juanjuan, Peng Ya, Tang Anliu, Li Nan, Zhou Weiwei, Wang Zeyou, Zhang Decai, Xiang Bo, Ge Jie, Li Guiyuan, Wu Minghua, Li Xiayu

机构信息

1 Department of Gastroenterology, The Third Xiangya Hospital, Central South University , Changsha, Hunan, People's Republic of China .

出版信息

OMICS. 2014 Jan;18(1):54-64. doi: 10.1089/omi.2012.0132. Epub 2013 Nov 16.

Abstract

Colorectal cancer (CRC) is a common malignant gastrointestinal cancer. Efforts for preventive and personalized medicine have intensified in the last decade with attention to novel forms of biomarkers. In the present study, microRNA and genetic analyses were performed in tandem for differential transcriptome profiling between primary tumors with or without nodes or distant metastases. Serial Test Cluster (STC) analysis demonstrated that 20 genes and two microRNAs showed distinctive expression patterns associated with the tumor, node, and metastasis (TNM) stage. The selected target genes were characterized by GO and Pathway analysis. A microRNA-target gene network analysis showed that miR-429 resided in the center of the network, indicating that miR-429 might serve important roles in the development of CRC. Real-time PCR and tissue microarrays showed that miR-429 had a dynamic expression pattern during the CRC progression stage, and was significantly downregulated in stage II and stage III clinical progression. The low expression of miR-429 was correlated with poor prognosis for CRC. Taken together, miR-429 warrant further clinical translation research as a candidate biomarker for CRC prognosis. Additional downstream targets and attendant gene function also need to be discerned to design a sound critical path to personalized medicine for persons susceptible to, or diagnosed with CRC.

摘要

结直肠癌(CRC)是一种常见的胃肠道恶性肿瘤。在过去十年中,随着对新型生物标志物形式的关注,预防医学和个性化医学的研究力度不断加大。在本研究中,对原发性肿瘤有无淋巴结或远处转移的差异转录组进行了串联的微小RNA和基因分析。系列测试聚类(STC)分析表明,20个基因和两个微小RNA表现出与肿瘤、淋巴结和转移(TNM)分期相关的独特表达模式。通过基因本体(GO)和通路分析对所选靶基因进行了表征。微小RNA-靶基因网络分析表明,miR-429位于网络中心,这表明miR-429可能在结直肠癌的发展中起重要作用。实时聚合酶链反应(PCR)和组织微阵列显示,miR-429在结直肠癌进展阶段具有动态表达模式,在临床进展的II期和III期显著下调。miR-429的低表达与结直肠癌的不良预后相关。综上所述,miR-429作为结直肠癌预后的候选生物标志物,值得进一步开展临床转化研究。还需要识别其他下游靶点及相关基因功能,以便为易患或已诊断为结直肠癌的患者设计出合理的个性化医疗关键路径。

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