基于基因芯片的前列腺癌转移高表达基因SPP1的生物信息学分析

The highly expressed secreted phosphoprotein 1 gene in prostate cancer metastasis:A microarray- based bioinformatic analysis

目的:利用生物信息学方法分析前列腺癌转移高表达基因SPP1以及蛋白的结构,为进一步研究其功能和参与的调控机制提供一定的理论依据。方法:在公共基因芯片数据库(GEO)中下载前列腺癌转移相关基因芯片数据,利用BRB-Array Tools软件、protparam、Motif Scan、Signal P4.0、TMHMM、Net Phos2.0、Predict Protein、GO、KEGG、STRING等生物信息学工具进行数据挖掘及生物信息学分析。结果:共筛选出前列腺癌转移共同差异基因73个,表达上调21个,表达下调52个(P<0.01),其中对前列腺癌转移高表达基因SPP1进行生物信息学分析发现,SPP1蛋白由314个氨基酸组成,该蛋白含有2个N-连接糖基化位点、8个酪蛋白激酶II磷酸化位点、3个PKC磷酸化位点,主要参与细胞外基质结合、骨化、成骨细胞分化、细胞黏附、PI3K-Akt信号通路、黏着斑、ECM受体相互作用、Toll样受体信号通路等分子功能和信号通路。结论:利用生物信息学的方法能有效分析基因芯片数据并获取生物内在信息,SPP1可能在前列腺癌转移中发挥重要作用,有望成为前列腺癌转移的早期诊断标志物和治疗的新靶点。

Objective： To investigate the composition,function,and regulatory mechanisms of the secreted phosphoprotein 1（ SPP1） gene in metastatic prostate cancer. Methods： We obtained the data about the whole genomic expression profiles on prostate cancer metastasis from the GEO database,and performed data-mining and bioinformatic analysis using BRB-Array Tools and such softwares as Protparam,Motif Scan,Signal P 4. 0,TMHMM,Net Phos2. 0,Predict Protein,GO,KEGG,and STRING. Results： Totally,73 co-expressed differential genes in prostate cancer metastasis were identified,21 up-regulated and 52 down-regulated（ P〈 0. 01）.Bioinformatic analysis indicated that the highly expressed SPP1 gene encoded 314 amino acids and contained 2 N-glycosylation sites,8casein kinase II phosphorylation sites and 3 protein kinase C phosphorylation sites,playing essential roles in extracellular matrix（ ECM） binding,ossification,osteoblast differentiation,cell adhesion,PI3K-Akt signaling pathway,focal adhesion,Toll-like receptor signaling pathway,and ECM-receptor interaction. Conclusion： The bioinformatic method showed a high efficiency in analyzing microarray data and revealing internal biological information. SPP1 may play an important role in prostate cancer metastasis and become a novel biomarker for the diagnosis of prostate cancer metastasis and a new target for its treatment.