本文選題：生物信息學(xué)　切入點(diǎn)：Meta　出處：《華中科技大學(xué)》2016年碩士論文

【摘要】：【目的】高級(jí)別漿液性卵巢癌(high-grade serous carcinomas,HGSC)不僅在臨床表現(xiàn)上呈現(xiàn)高度的異質(zhì)性,在分子水平也是如此,因此本文從公共數(shù)據(jù)庫(kù)分析入手,找到并驗(yàn)證卵巢癌轉(zhuǎn)移相關(guān)基因�！痉椒ā坑肦語(yǔ)言分析已共享的HGSC的表達(dá)譜芯片,分析出轉(zhuǎn)移灶相對(duì)于原位灶的差異基因;采用Bioconductor中的curated Ovarian Data包,對(duì)全基因組每個(gè)基因進(jìn)行meta分析,獲得該基因與無(wú)進(jìn)展生存(PFS)的HR值及其p值;將芯片分析的差異基因和meta分析的結(jié)果合并后,按照綜合效應(yīng)得出了候選基因,并在臨床標(biāo)本上驗(yàn)證�！窘Y(jié)果】表達(dá)譜芯片GSE2109共有222例,剔除掉非HGSC后剩余124例,在R語(yǔ)言中通過(guò)質(zhì)控剔除不合格芯片后剩余90例。其中HGSC原位灶共62例,網(wǎng)膜轉(zhuǎn)移灶共28例。采用gcrma方式標(biāo)準(zhǔn)化后,本文用SAM檢驗(yàn)得到差異基因若干。通過(guò)R語(yǔ)言包c(diǎn)urated Ovarian Data篩選出7個(gè)包含PFS臨床信息的數(shù)據(jù)集,并用meta分析獲得全部基因?qū)FS的風(fēng)險(xiǎn)比(Hazard Ratio,HR)值及其p值。將差異基因和Gene Meta的結(jié)果綜合分析后,得到了在原位和轉(zhuǎn)移灶差異表達(dá)且與臨床預(yù)后相關(guān)的基因,且這兩種數(shù)據(jù)具有很好的線(xiàn)性關(guān)系。這些基因的top100通過(guò)pathway分析確認(rèn)其主要富集在轉(zhuǎn)移相關(guān)通路。取前12的基因設(shè)計(jì)引物后在本院臨床標(biāo)本中進(jìn)行驗(yàn)證,所得結(jié)論與前述相符�！窘Y(jié)論】采用生物信息學(xué)加臨床驗(yàn)證的方式挑選出的轉(zhuǎn)移相關(guān)基因,且從統(tǒng)計(jì)學(xué)和臨床標(biāo)本的角度驗(yàn)證了這些結(jié)果。這些基因可能參與了HGSC的侵襲轉(zhuǎn)移過(guò)程。對(duì)于臨床的意義在于,對(duì)其干預(yù)可能阻止腫瘤的侵襲轉(zhuǎn)移,也可以作為腫瘤發(fā)生轉(zhuǎn)移的分子標(biāo)志,或者可以用來(lái)對(duì)預(yù)后進(jìn)行評(píng)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.
【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類(lèi)號(hào)】：R737.31

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