本文選題：肝癌 + 差異表達(dá)基因　； 參考：《重慶醫(yī)科大學(xué)》2017年碩士論文

【摘要】：第一部分肝癌差異表達(dá)基因的生物信息學(xué)分析目的:通過生物信息學(xué)方法分析HCC(Hepatocellular Carcinoma)肝癌相關(guān)差異表達(dá)基因,篩選HCC判斷預(yù)后的分子標(biāo)志物和免疫治療的潛在分子靶點。方法:應(yīng)用公共基因表達(dá)數(shù)據(jù)庫(Gene Expression Omnibus,GEO)下載肝癌相關(guān)芯片數(shù)據(jù),采用JMP軟件進(jìn)行GSE數(shù)據(jù)集相關(guān)性分析,使用R語言中的Limma程序篩選差異表達(dá)基因,并對差異表達(dá)基因進(jìn)行GO(Gene Ontology)富集分析、KEGG(Kyoto Encyclopedia of Genes and Genomes)通路分析及蛋白互作(protein-protein interaction,PPI)調(diào)控網(wǎng)絡(luò)構(gòu)建。同時聯(lián)合TCGA數(shù)據(jù)庫中其他腫瘤RNA-Seq轉(zhuǎn)錄組數(shù)據(jù)進(jìn)行HCC特異性表達(dá)分析,進(jìn)一步篩選HCC特異差異表達(dá)基因。結(jié)果:MBL2、SDS、SLCO1B3、TDO2、SAA4、SPP2在HCC中特異性表達(dá)下調(diào),GPC3基因在肝癌中表達(dá)上調(diào),只有SPP2的表達(dá)與患者的生存期正相關(guān)。結(jié)論:GPC3基因可作為HCC免疫治療的潛在分子靶點,SPP2有望成為判斷肝癌患者預(yù)后的標(biāo)志物。第二部分CSMD2在肝癌中的作用初探目的:對CSMD2基因進(jìn)行系統(tǒng)進(jìn)化分析和功能注釋,檢測其在HCC組織和癌旁組織中的表達(dá),并探討CSMD2在HCC中的作用。方法:通過NCBI數(shù)據(jù)庫檢索CSMD2序列,采用Tree Fam網(wǎng)站構(gòu)建CSMD2系統(tǒng)進(jìn)化樹,對CSMD2進(jìn)行功能注釋,q RT-PCR技術(shù)及免疫組化方法分別檢測CSMD2在HCC組織的表達(dá),分析CSMD2在不同臨床病理特征HCC病人的表達(dá)情況。結(jié)果:在RNA水平上,CSMD2在癌旁組織中的表達(dá)高。免疫組化方法檢測,CSMD2在癌旁組織中陽性表達(dá)率為52.0%,在HCC組織的陽性表達(dá)率為84.0%。CSMD2在肝癌組織內(nèi)的表達(dá)與患者的性別、年齡、術(shù)前AFP、巴塞羅那分期、病理分級、HBs Ag陽性與否,腫瘤的大小及數(shù)目等無相關(guān)性,CSMD2在HCC患者的表達(dá)缺失與患者的淋巴結(jié)轉(zhuǎn)移正相關(guān)(p0.05)。結(jié)論:CSMD2的表達(dá)缺失可能導(dǎo)致HCC的轉(zhuǎn)移。
[Abstract]:Part I Bioinformatics Analysis of differentially expressed genes in Hepatocellular carcinoma objective: to analyze the differentially expressed genes related to HCC(Hepatocellular carcinoma by bioinformatics, and to screen the molecular markers for predicting the prognosis of HCC and the potential molecular targets for immunotherapy. Methods: using common gene expression database (Gene Expression Omnibus GE) to download liver cancer related chip data, JMP software was used to analyze the correlation of GSE data sets, and Limma program in R language was used to screen differentially expressed genes. The differentially expressed genes were analyzed by GO(Gene Ontology) enrichment analysis and the construction of protein interaction protein-protein interaction (PPI) regulatory network. At the same time, HCC specific expression was analyzed with other tumor RNA-Seq transcriptional data in TCGA database to further screen HCC specific differentially expressed genes. Results the specific expression of TDO2SAA4SPP2 in HCC was down-regulated. The expression of GPC3 gene was up-regulated in HCC. Only the expression of SPP2 was positively correlated with the survival time of the patients. Conclusion the molecular target of HCC immunotherapy, SPP2, may be a potential marker for predicting the prognosis of HCC patients. Part two the role of CSMD2 in hepatocellular carcinoma objective: to investigate the expression of CSMD2 gene in HCC and adjacent tissues, and to explore the role of CSMD2 in HCC by phylogenetic analysis and functional annotation. Methods: CSMD2 sequences were retrieved from NCBI database, and CSMD2 phylogenetic tree was constructed by Tree Fam website. The expression of CSMD2 in HCC tissues was detected by using q-RT-PCR technique and immunohistochemical method, respectively. To analyze the expression of CSMD2 in HCC patients with different clinicopathological features. Results: the expression of CSMD2 in paracancerous tissues was high at RNA level. Immunohistochemical method was used to detect the positive expression rate of CSMD2 in paracancerous tissues (52.0%), and the positive expression rate of 84.0%.CSMD2 in HCC tissues was the same as sex, age, preoperative AFP, Barcelona stage, pathological grade and HBs Ag positive or not. There was no correlation between the size and number of tumors and the loss of CSMD2 expression in patients with HCC. There was a positive correlation between the loss of CSMD2 expression and lymph node metastasis (p0.05). Conclusion the loss of the expression of HCC might lead to the metastasis of HCC.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R735.7

【參考文獻(xiàn)】

相關(guān)期刊論文 前4條

1 陳萬勇;張文韜;周晨浩;沈英皓;劉彬彬;任寧;;CSMD1基因rs1613815基因型與肝細(xì)胞肝癌臨床病理特征的關(guān)系[J];復(fù)旦學(xué)報(醫(yī)學(xué)版);2016年03期

2 Yukihiro Haruyama;Hiroaki Kataoka;;Glypican-3 is a prognostic factor and an immunotherapeutic target in hepatocellular carcinoma[J];World Journal of Gastroenterology;2016年01期

3 朱喬;陳春偉;鞏麗;姚麗;韓秀娟;朱少君;蘭淼;張佳瑞;任拼;張偉;;CSMD1在肝細(xì)胞肝癌中的研究進(jìn)展[J];現(xiàn)代腫瘤醫(yī)學(xué);2014年11期

4 Jia Li;Jian-Zhi Gao;Jing-Li Du;Li-Xin Wei;;Prognostic and clinicopathological significance of glypican-3 overexpression in hepatocellular carcinoma: A meta-analysis[J];World Journal of Gastroenterology;2014年20期

相關(guān)博士學(xué)位論文 前2條

1 王再興;六個新的尋常型銀屑病易感基因的鑒定[D];安徽醫(yī)科大學(xué);2010年

2 李建伏;基于DNA序列的進(jìn)化樹構(gòu)建算法的研究[D];哈爾濱工業(yè)大學(xué);2008年

相關(guān)碩士學(xué)位論文 前2條

1 孫海波;CSMD1基因和BRG1基因與喉鱗狀細(xì)胞癌發(fā)生的相關(guān)性研究[D];吉林大學(xué);2012年

2 唐志學(xué);種系發(fā)生樹構(gòu)建算法的研究[D];哈爾濱工業(yè)大學(xué);2006年

，

本文編號：1934934