microRNAs调控基质金属蛋白酶与乳腺癌发生发展和转移的生物信息学分析

Bioinformatics analysis of microRNAs regulation of matrix metalloproteinases in the occurrence, progression and metastasis of breast cancer

摘要:

目的： 利用生物信息学方法研究microRNAs调控基质金属蛋白酶（matrix metalloproteinases，MMPs）乳腺癌的潜在靶向基因、信号传导通路及分子机制。方法： 从GEO和TCGA数据库下载正常乳腺组织和乳腺癌样本的基因芯片；使用R软件包limma分析正常乳腺组织和乳腺癌样本之间的差异表达基因；对筛选出的差异表达基因进行KEGG信号通路富集分析。结果： 通过对差异基因的趋势分析，筛选出544个显著上调的基因及1 030个显著下调的基因，其中MMP1/3/9/11/13/28可能为介导乳腺癌浸润性进展的相关基因。生存分析表明，乳腺癌MMP1/3/9/11/13高表达与不良预后相关，且MMP1高表达是影响乳腺癌的独立危险因素（P<0.01）。结论： 本研究的整合生物信息学分析表明，MMPs在乳腺癌等多种癌组织中表达升高，并且MMPs表达明显影响乳腺癌患者预后，与其他MMPs相比，MMP1可能是乳腺癌患者靶向治疗的合适靶点。

Abstract:

Objective: To explore the potential target genes, signal transduction pathways and molecular mechanisms of MicroRNAs regulating matrix metalloproteinases (MMPs) in breast cancer using bioinformatics analysis. Methods: Gene chips samples of normal mammary gland tissues and breast cancer tissues were downloaded from GEO database and TCGA database. The differentially expressed genes between normal tissue samples and breast cancer tissues were analyzed by R software package Limma. KEGG pathway analysiswas performed for the screened differentially expressed genes. Results: Through trend analysis of differentially expressed genes, 544 significantly up-regulated genes and 1 030 significantly down-regulated genes were screened, among which MMP1/3/9/11/13/28 could be related genes that mediate invasive progression of breast cancer. Survival analysis showed that the high expression of MMP1/3/9/11/13 was associated with poor prognosis, and the high expression of MMP1 was an independent risk factor for breast cancer (P<0.01). Conclusion: The integrative bioinformatics analysis performed in the present study suggests that the expression of MMPs is increased in breast cancer and other cancer tissues, and the expression of MMPs can significantly affect the prognosis of breast cancer patients. Compared with other MMPs, MMP1 may be an appropriate target for targeted therapy in patients with breast cancer.