基于高通量基因表达数据库开发骨肉瘤预后相关的微小RNA研究

Development of microRNA related to the prognosis of osteosarcoma based on GEO database

目的筛选骨肉瘤失调微小RNA(microRNA),构建多基因预后模型,探索骨肉瘤的关键microRNA治疗靶标。方法通过高通量基因表达数据库(gene expression omnibus, GEO)中的GSE28423数据集,筛选相对于癌旁正常组织和骨肉瘤组织中的差异microRNA,并利用GSE39040数据集中的临床信息,分析这些差异microRNA对预后生存的影响;对关键microRNA的靶基因进行功能富集,探索关键microRNA的功能,构建基于关键microRNA的预后预测模型。结果共获得共166个差异microRNA,其中70个下调,96个上调(P<0.05),其中有3个microRNA对患者的总体生存率以及预后有显著影响(P<0.05),分别是hsa–miR–1、hsa–miR–153和hsa–miR–487b。构建由hsa–mi R–1、hsa–miR–153和hsa–miR–487b共同组成的预后预测模型,ROC结果显示该模型具有良好的预后预测性能(AUC=0.842 8,95%CI:0.741 7~0.943 9,P<0.000 1);功能富集分析也提示,hsa–miR–1、hsa–miR–153和hsa–mi R–487b所调控的靶基因,富集于细胞增殖、凋亡和上皮间充质转化等多个与肿瘤相关的功能(P<0.05)。结论has–mi R–1、has–miR–153和has–miR–487b可能在骨肉瘤的发生发展过程中发挥重要作用,并有望成为骨肉瘤生物分子标志物及治疗靶点。

Objective To screen the dysregulated microRNA in osteosarcoma, construct a multi–gene prognostic model, and explore the key miRNA targets for the treatment of osteosarcoma. Methods Through the GSE28423 dataset in the GEO database, the differential microRNAs in osteosarcoma tissues compared to cancer –adjacent normal tissues were screened, and the clinical parameters of the GSE39040 dataset were used to analyze the impact of these d ifferential microRNAs on the prognosis and the function of key microRNAs enrichment, explore the functions of key microRNAs, and construct prognostic prediction models based on key microRNAs. Results A total of 166 differential microRNAs were obtained, of which 70 were down–regulated and 96 were up–regulated(P<0.05). A total of three microRNAs had a significant impact on the overall survival rate and prognosis of patients(P<0.05), namely, hsa–miR–1, hsa–miR–153 and hsa–miR–487b. A prognostic prediction model consisting of hsa–miR–1, hsa–miR–153 and hsa–miR–487b was constructed. The ROC(AUC=0.842 8, 95%CI: 0.741 7–0.943 9, P<0.000 1) results showed this model had good performance. Functional enrichment analysis also suggestsed that the target genes regulated by hsa–miR–1, hsa–miR–153 and hsa–miR–487b were enriched in cell proliferation, apoptosis, epithelial–mesenchymal transformation, etc.(P< 0.05). Conclusions The hsa–miR–1, hsa–miR–153 and hsa–miR–487b may play an important role in the occurrence and development of osteosarcoma, and they are expected to be the potential application value of diagnostic biomolecular markers and therapeutic targets for osteosarcoma.