多数据库联合分析卵巢癌转移相关基因

发布时间：2018-04-01 13:27

本文选题：生物信息学　切入点：Meta　出处：《华中科技大学》2016年硕士论文

【摘要】：【目的】高级别浆液性卵巢癌(high-grade serous carcinomas,HGSC)不仅在临床表现上呈现高度的异质性,在分子水平也是如此,因此本文从公共数据库分析入手,找到并验证卵巢癌转移相关基因。【方法】用R语言分析已共享的HGSC的表达谱芯片,分析出转移灶相对于原位灶的差异基因;采用Bioconductor中的curated Ovarian Data包,对全基因组每个基因进行meta分析,获得该基因与无进展生存(PFS)的HR值及其p值;将芯片分析的差异基因和meta分析的结果合并后,按照综合效应得出了候选基因,并在临床标本上验证。【结果】表达谱芯片GSE2109共有222例,剔除掉非HGSC后剩余124例,在R语言中通过质控剔除不合格芯片后剩余90例。其中HGSC原位灶共62例,网膜转移灶共28例。采用gcrma方式标准化后,本文用SAM检验得到差异基因若干。通过R语言包curated Ovarian Data筛选出7个包含PFS临床信息的数据集,并用meta分析获得全部基因对PFS的风险比(Hazard Ratio,HR)值及其p值。将差异基因和Gene Meta的结果综合分析后,得到了在原位和转移灶差异表达且与临床预后相关的基因,且这两种数据具有很好的线性关系。这些基因的top100通过pathway分析确认其主要富集在转移相关通路。取前12的基因设计引物后在本院临床标本中进行验证,所得结论与前述相符。【结论】采用生物信息学加临床验证的方式挑选出的转移相关基因,且从统计学和临床标本的角度验证了这些结果。这些基因可能参与了HGSC的侵袭转移过程。对于临床的意义在于,对其干预可能阻止肿瘤的侵袭转移,也可以作为肿瘤发生转移的分子标志,或者可以用来对预后进行评估。
[Abstract]:[objective] High-grade serous ovarian cancer high-grade serous carcinomas HGSCs not only present high heterogeneity in clinical manifestations, but also at molecular level.To identify and verify the metastasis related genes of ovarian cancer. [methods] using R language to analyze the shared HGSC expression microarray, to analyze the differentially expressed genes between metastatic foci and in situ foci, and to use the curated Ovarian Data package in Bioconductor.The HR value and p value of each gene in the whole genome were obtained by meta analysis, and the candidate genes were obtained by combining the differential genes of microarray analysis with the results of meta analysis.[results] A total of 222 cases of expression microarray GSE2109, 124 cases after excluding non-#en1#, and 90 cases in R language after removing unqualified chip by quality control.62 cases of HGSC in situ and 28 cases of omentum metastasis.After standardization by gcrma, several differentially expressed genes were obtained by SAM test.Through R language package curated Ovarian Data, 7 data sets containing PFS clinical information were selected, and the risk ratio of all genes to PFS and its p value were obtained by meta analysis.By synthesizing the results of differential gene and Gene Meta, the differentially expressed genes in situ and metastatic foci were obtained, which were related to clinical prognosis, and the two data had a good linear relationship.The top100 of these genes was confirmed by pathway analysis to be mainly concentrated in metastasis related pathways.The primer design of the first 12 genes was used to verify the results in clinical specimens of our hospital. [conclusion] Metastasis-related genes selected by bioinformatics and clinical verification were selected.These results were validated from the statistical and clinical point of view.These genes may be involved in the invasion and metastasis of HGSC.The clinical significance is that intervention may prevent tumor invasion and metastasis, may be used as a molecular marker of tumor metastasis, or can be used to evaluate prognosis.
【学位授予单位】：华中科技大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R737.31

【相似文献】