前列腺癌差异表达基因的筛选及相互作用的生物信息学分析

发布时间：2018-01-29 13:06

本文关键词： 前列腺癌基因芯片差异基因生物信息学　出处：《中国癌症杂志》2017年03期 　论文类型：期刊论文

【摘要】：背景与目的:基因芯片技术是利用杂交测序方法,可大规模高通量地检测不同组织、细胞中的基因表达水平的技术。该研究采用基因芯片技术筛选前列腺癌及前列腺炎症穿刺组织中差异表达的基因并对其进行生物学信息分析。方法:采用美国Affymetrix Human U133 plus 2.0基因表达谱芯片,按一步法分别抽提恶性程度较高的前列腺癌及前列腺炎症组织的总RNA,并分离纯化这两种组织的m RNA。经逆转录合成掺入生物素标记的c DNA合成探针,与芯片杂交和严格洗片后,用荧光扫描仪扫描芯片荧光信号图像。用生物信息学方法分析前列腺癌及前列腺炎症组织中差异表达基因。结果:按照表达差异倍数大于等于2,P0.05的筛选条件,筛选出差异基因1 819条,其中上调表达基因1 025条和下调表达基因794条。采用GO富集分析发现这些差异基因主要涉及细胞周期、分子代谢等分子功能以及生物学过程;KEGG信号通路分析发现,这些差异基因主要涉及嘌呤核苷酸代谢等代谢通路。STING在线工具分析对差异基因编码的蛋白质间的相互作用进行分析,结果发现这些基因编码的蛋白间的相互作用主要集中在TPX2、ANLN、NUSAP1、MELK、DLGAP5、KIF11、TOP2A及RRM2等20个关键节点基因。最后对重要节点基因进行文献挖掘,发现CEP55和ANLN基因可能与前列腺癌的发生和转移有关。结论:在前列腺癌的发生、发展中,促使细胞进入增殖周期的相关基因的活化、代谢相关酶类基因活性的异常、细胞黏附功能相关基因的抑制以及细胞移行相关基因的激活等因素发挥了重要的作用。系统的分析这些基因发现,CEP55和ANLN基因与前列腺癌的发生和预后关系密切,为下一步研究实验提供有价值的线索。进一步研究相关差异基因将有望发现新的早期诊断指标,为建立个体化治疗方案和预后评估系统提供帮助。
[Abstract]:Background & objective: gene chip technology is a large scale high-throughput detection of different tissues by hybridization and sequencing. Techniques for gene expression levels in cells. Gene microarray techniques were used to screen differentially expressed genes in prostate cancer and prostatic inflammatory puncture tissues and to analyze their biological information. Affymetrix Human U133 plus 2.0 gene expression microarray was used. Total RNA was extracted from prostate cancer and prostatic inflammatory tissues with high malignancy by one step method. The mRNAs of the two tissues were isolated and purified. The biotin labeled c DNA synthesis probe was synthesized by reverse transcription and then hybridized with the microarray and washed strictly. Fluorescence scanner was used to scan the microarray fluorescence signal image and bioinformatics method was used to analyze the differentially expressed genes in prostate cancer and prostatic inflammation. The screening conditions of P0.05, screening out the difference gene 1,819. Among them, 1025 up-regulated genes and 794 down-regulated genes were found to be involved in cell cycle, molecular metabolism and biological processes by go enrichment analysis. KEGG signaling pathway analysis showed that these differentially expressed genes were mainly involved in metabolic pathways such as purine nucleotide metabolism. The results showed that the interaction between the proteins encoded by these genes was mainly concentrated in TPX2ANLNNN Nu SAP1 MELKN DLGAP5KIF11. There are 20 key node genes such as TOP2A and RRM2. Finally, the important node genes are mined. It is found that CEP55 and ANLN genes may be related to the occurrence and metastasis of prostate cancer. Conclusion: during the occurrence and development of prostate cancer, the activation of genes related to the cell into the proliferative cycle. The abnormal activity of metabolism-related enzymes, the inhibition of genes associated with cell adhesion and the activation of genes associated with cell migration play an important role. CEP55 and ANLN genes are closely related to the occurrence and prognosis of prostate cancer, which provides valuable clues for further research. To provide assistance for the establishment of individualized treatment regimen and prognosis evaluation system.
【作者单位】：复旦大学附属公共卫生临床中心医学检验科;上海交通大学附属第六人民医院南院泌尿外科;复旦大学附属中山医院泌尿外科;复旦大学附属中山医院病理科;复旦大学附属公共卫生临床中心感染控制科;
【基金】：国家自然科学基金面上项目(81372318) 上海市2014年度“科技创新行动计划”实验动物研究领域科技支撑项目重点项目(14140901400) 上海市自然科学基金项目(13ZR1435000)
【分类号】：R737.25
【正文快照】： 前列腺癌在许多欧美国家是男性最常见的关的差异表达基因进行筛选分析。本实验应用恶性肿瘤之一,其死亡率仅次于肺癌,居男性基因芯片技术检测了恶性程度较高的前列腺癌肿瘤的第二位[1]。虽然我国前列腺癌的发病率和前列腺炎症穿刺组织中基因表达的不同,初较低,但随着我国人口

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