构建和综合分析ceRNA网络以揭示三阴性乳腺癌潜在的新型生物标志物
Construction and Comprehensive Analysis of a ceRNA Network to Reveal Potential Novel Biomarkers for Triple-Negative Breast Cancer.
作者信息
Ma Lifei, Song Guiqin, Li Meiyu, Hao Xiuqing, Huang Yong, Lan Jinping, Yang Siqian, Zhang Zetian, Zhang Guohui, Mu Jiao
机构信息
College of Laboratory Medicine, Hebei North University, Zhangjiakou, Hebei 075000, People's Republic of China.
State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, People's Republic of China.
出版信息
Cancer Manag Res. 2020 Aug 7;12:7061-7075. doi: 10.2147/CMAR.S260150. eCollection 2020.
BACKGROUND
Triple-negative breast cancer (TNBC) is the most common and aggressive type of breast cancer with an unfavourable outcome worldwide. Novel therapeutic targets are urgently required to explore this malignancy. This study explored the ceRNA network and the important genes for predicting the therapeutic targets.
METHODS
It identified the differentially expressed genes of mRNAs, lncRNAs and miRNAs between TNBC and non-TNBC samples in four cohorts (TCGA, GSE38959, GSE45827 and GSE65194) to explore the novel therapeutic targets for TNBC. Downstream analyses, including functional enrichment analysis, ceRNA network, protein-protein interaction and survival analysis, were then conducted by bioinformatics analysis. Finally, the potential core protein of the ceRNA network in TNBC was validated by immunohistochemistry.
RESULTS
A total of 1,045 lncRNAs and 28 miRNAs were differentially expressed in the TCGA TNBC samples, and the intersections of 282 mRNAs (176 upregulations and 106 downregulations) between the GEO and TCGA databases were identified. A ceRNA network composed of 7 lncRNAs, 62 mRNAs, 12 miRNAs and 244 edges specific to TNBC was established. The functional assay showed dysregulated genes, and GO, DO and KEGG enrichment analysis were performed. Survival analysis showed that mRNA and lncRNA were significantly correlated with the overall survival of patients with TNBC in the TCGA databases (P < 0.05). Finally, the protein was validated, and immunohistochemical results showed the upregulated expression of in TNBC tissues.
CONCLUSION
Thus, our study presents an enhanced understanding of the ceRNA network in TNBC, where the key gene may be a new promising potential therapeutic target for patients with TNBC.
背景
三阴性乳腺癌（TNBC）是全球最常见且侵袭性最强的乳腺癌类型，预后不佳。迫切需要探索新的治疗靶点来攻克这种恶性肿瘤。本研究探索了ceRNA网络以及预测治疗靶点的重要基因。
方法
在四个队列（TCGA、GSE38959、GSE45827和GSE65194）中鉴定TNBC和非TNBC样本之间mRNA、lncRNA和miRNA的差异表达基因，以探索TNBC的新治疗靶点。然后通过生物信息学分析进行下游分析，包括功能富集分析、ceRNA网络分析、蛋白质-蛋白质相互作用分析和生存分析。最后，通过免疫组织化学验证TNBC中ceRNA网络的潜在核心蛋白。
结果
在TCGA的TNBC样本中，共有1045个lncRNA和28个miRNA差异表达，并且鉴定出了GEO和TCGA数据库之间282个mRNA（176个上调和106个下调）的交集。建立了一个由7个lncRNA、62个mRNA、12个miRNA和244条边组成的TNBC特异性ceRNA网络。功能分析显示基因失调，并进行了基因本体论（GO）、疾病本体论（DO）和京都基因与基因组百科全书（KEGG）富集分析。生存分析表明，在TCGA数据库中，mRNA和lncRNA与TNBC患者的总生存期显著相关（P<0.05）。最后，对该蛋白进行了验证，免疫组织化学结果显示TNBC组织中该蛋白表达上调。
结论
因此，我们的研究加深了对TNBC中ceRNA网络的理解，其中关键基因可能是TNBC患者新的有前景的潜在治疗靶点。
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