本文選題：前列腺癌 + 轉(zhuǎn)錄組測(cè)序�。� 參考：《南昌大學(xué)》2014年碩士論文

【摘要】：前列腺癌是男性的世界第二大最常見(jiàn)的癌癥，而每年的發(fā)病率有增加的趨勢(shì)。所有的男性都可能罹患前列腺癌，這些情況值得引起重視。全世界范圍內(nèi)來(lái)說(shuō)，約1/6的男性可能被診斷出前列腺癌，而在這1/6的男性中，1/36的人因此死亡。雖然，亞洲男性，，尤其是中國(guó)男性，相對(duì)于歐美男性的發(fā)病率要低很多，但是近年來(lái)中國(guó)男性的前列腺癌越來(lái)越呈多發(fā)趨勢(shì)，已經(jīng)成為了危害我國(guó)中老年男性的重要疾病之一。 隨著測(cè)序數(shù)據(jù)大規(guī)模產(chǎn)生，腫瘤的發(fā)生與發(fā)展，不論是在細(xì)胞水平，還是在分子水平的變化上，科學(xué)家們對(duì)此都有了更深刻的認(rèn)識(shí)，即前列腺癌是一種有多基因共同作用的復(fù)雜的癌癥。其中PI3K/AKT/MTOR途徑，WNT途徑，TGF-β/SMAD途徑表達(dá)的改變，可能可以增強(qiáng)腫瘤細(xì)胞的生長(zhǎng)，轉(zhuǎn)移和侵襲能力，尤其是PI3K/AKT/MTOR途徑，在前列腺癌中具有很重要的作用。但遺憾的是，目前科學(xué)家對(duì)于前列腺癌發(fā)生發(fā)展過(guò)程中的機(jī)制了解還不夠深入。所以，研究前列腺癌與其他癌癥之間的異同，可以為前列腺癌的發(fā)生發(fā)展提供重要基因水平的依據(jù)。 同時(shí)，前列腺癌的早期診斷在前列腺癌的治療中具有非常重要的臨床意義。PSA（prostate specific antigen，前列腺特異抗原）是目前廣泛用于檢測(cè)前列腺癌的重要標(biāo)志物。但是PSA并非腫瘤特異的標(biāo)志物，前列腺炎癥的發(fā)生也會(huì)導(dǎo)致PSA檢測(cè)陽(yáng)性。因此，我們有必要篩選出更加特異、有效的靶分子。 在基因芯片，測(cè)序技術(shù)的產(chǎn)生，使得一次性檢測(cè)成千上萬(wàn)個(gè)基因的表達(dá)譜成為可能。傳統(tǒng)單基因的分析方法已經(jīng)被淘汰了。而隨著越來(lái)越多的數(shù)據(jù)的產(chǎn)生，對(duì)生物信息學(xué)分析方法提出了更高的要求，迫使科學(xué)家們必須使用生物信息學(xué)將海量的數(shù)據(jù)整合，分析，并從中篩選出合適的基因，并必須揭示海量的基因與復(fù)雜的生物學(xué)功能之間可能存在的聯(lián)系。 為此，本研究使用了測(cè)序，芯片的方法，結(jié)合WGCNA共表達(dá)網(wǎng)絡(luò)分析，GO，KEGG等生物學(xué)功能數(shù)據(jù)庫(kù)，試圖為今后前列腺癌的研究，提供一些新的觀點(diǎn)。 【目的】本研究利用R語(yǔ)言中的bioconductor中的WGCNA （Weighted GeneCo-expression Network Analysis,加權(quán)基因共表達(dá)網(wǎng)絡(luò)分析）分析包對(duì)來(lái)自于基因表達(dá)數(shù)據(jù)庫(kù)GEO（Gene Expression Omnibus）中分別來(lái)源于兩篇文獻(xiàn)，共40個(gè)前列腺癌癥RNA-seq數(shù)據(jù)（Gleason score6），20個(gè)前列腺癌旁組織RNA-seq數(shù)據(jù)（normal），以及16個(gè)肺癌RNA-seq數(shù)據(jù)，3個(gè)肝癌以及對(duì)應(yīng)的3個(gè)癌旁組織RNA-seq數(shù)據(jù)，10個(gè)急性白血病RNA-seq數(shù)據(jù)，5個(gè)乳頭狀腎癌RNA-seq數(shù)據(jù)做生物信息學(xué)分析，并隨后使用5種前列腺癌癥常用細(xì)胞系:PrEC、PWRE、DU145、LNCaP、VCaP的RNA-seq數(shù)據(jù)進(jìn)行比對(duì)。并使用了約600個(gè)affymatrix PLUS2.0A芯片數(shù)據(jù)，以及1000個(gè)TCGA RNA-SEQ測(cè)序數(shù)據(jù)進(jìn)行驗(yàn)證。在數(shù)據(jù)比對(duì)的基礎(chǔ)上，利用Cytoscape軟件，GO,KEGG,Rectome等數(shù)據(jù)庫(kù)，對(duì)數(shù)據(jù)的生物學(xué)意義進(jìn)行深入分析。為了了解前列腺癌與其他組織癌癥之間的關(guān)系，通過(guò)系統(tǒng)的研究特異表達(dá)基因的轉(zhuǎn)錄調(diào)控網(wǎng)絡(luò)，以及相關(guān)的生物學(xué)通路，從而更深入的探討前列腺癌癥組織中特異表達(dá)的基因的變化以及相關(guān)的生物學(xué)特性，闡述前列腺癌癥的發(fā)展的分子機(jī)制。本研究希望可以使用現(xiàn)有的數(shù)據(jù)庫(kù)，更好的使用現(xiàn)有的生物信息學(xué)手段，從而發(fā)現(xiàn)前列腺癌中特異表達(dá)的生物標(biāo)記物，探討前列腺癌區(qū)別于其他癌癥而發(fā)生發(fā)展的分子機(jī)制，因此本研究具有重要的現(xiàn)實(shí)意義。為進(jìn)一步了解前列腺癌發(fā)生發(fā)展的分子機(jī)制以及診斷治療提供了有用的基礎(chǔ)研究資料。 【結(jié)果】 1.前列腺癌癥組織數(shù)據(jù)與前列腺癌細(xì)胞系數(shù)據(jù)之間的結(jié)果差別迥異，沒(méi)有WGCNA特異表達(dá)基因modules的交集，說(shuō)明細(xì)胞系與前列腺臨床組織樣本之間存在很大的差異。 2.從發(fā)表自cellres上的文章中的前列腺癌RNA-SEQ數(shù)據(jù)中篩選出了388個(gè)特異表達(dá)基因。從發(fā)表自PNAS上的文章中的前列腺癌RNA-SEQ數(shù)據(jù)篩選出了238個(gè)特異表達(dá)基因，其中兩個(gè)集合的交集有8個(gè)基因，也就是說(shuō)，在轉(zhuǎn)移性前列腺癌中有8個(gè)基因是穩(wěn)定的表達(dá)出來(lái)了。 3.使用芯片數(shù)據(jù)，TCGA數(shù)據(jù)進(jìn)行驗(yàn)證，對(duì)所有特異表達(dá)結(jié)果進(jìn)行了GO和KEGG網(wǎng)絡(luò)分析。我們發(fā)現(xiàn)，不論在任何的前列腺癌癥數(shù)據(jù)中，PI3K/Akt/mTOR途徑發(fā)揮著至關(guān)重要的作用。與其同時(shí)，還發(fā)現(xiàn)了TGF-β/SMAD途徑，黏多糖功能途徑，胞外結(jié)構(gòu)組織功能途徑，notch途徑，一些神經(jīng)功能途徑與PI3K途徑同時(shí)發(fā)生。
[Abstract]:Prostate cancer is the second most common cancer in the world, and the incidence is increasing every year. All men are likely to suffer from prostate cancer. These are worthy of attention. Around the world, about 1/6 of men may be diagnosed with prostate cancer, and in this 1/6 male, 1/36 people die. Although, although, The incidence of Asian men, especially Chinese men, is much lower than that of men in Europe and America. However, in recent years, Chinese male prostate cancer is becoming more and more frequent and has become one of the most important diseases that endanger middle and old men in China.
With the large-scale production of sequencing data and the occurrence and development of the tumor, whether it is at the cell level or at the molecular level, the scientists have a deeper understanding that the prostate cancer is a complex cancer with multi gene interaction. The expression of the PI3K/AKT /MTOR pathway, the WNT pathway, and the TGF- beta /SMAD pathway It may enhance the growth, metastasis and invasion of tumor cells, especially the PI3K/AKT/MTOR pathway, which plays an important role in prostate cancer. But unfortunately, scientists are not well aware of the mechanism in the development of prostate cancer. So, the study of the similarities and differences between prostate cancer and other cancers can be done. It provides important gene level for the development of prostate cancer.
At the same time, the early diagnosis of prostate cancer has a very important clinical significance in the treatment of prostate cancer (prostate specific antigen, prostatic specific antigen) is an important marker for the detection of prostate cancer. But PSA is not a tumor specific marker, and the occurrence of prostatitis will also lead to the positive detection of PSA. Therefore, it is necessary for us to screen out more specific and effective target molecules.
The production of gene chips and sequencing technology makes it possible to detect the expression profiles of thousands of genes at one time. The traditional single gene analysis method has been eliminated. And as more and more data are produced, higher requirements for bioinformatics analysis have been put forward, forcing scientists to use bioinformatics. Massive data integration, analysis, and screening of appropriate genes, and must reveal the possible link between massive genes and complex biological functions.
To this end, this study uses sequencing, chip methods, combined with WGCNA to co express network analysis, GO, KEGG and other biological functional databases, trying to provide some new ideas for future research on prostate cancer.
[Objective] to use the WGCNA (Weighted GeneCo-expression Network Analysis, weighted gene co expression network analysis) in the Bioconductor of R language, the analysis packet from the gene expression database GEO (Gene Expression Omnibus) from two documents, 40 prostate cancer RNA-seq data, 20 RNA-seq data (normal), 16 RNA-seq data of lung cancer, 3 hepatoma and 3 corresponding paraplastic tissue RNA-seq data, 10 RNA-seq data for acute leukemia, 5 RNA-seq data of papillary renal carcinoma, and 5 common prostate cancer cell lines: PrEC, PWRE, DU145, LNCaP, VCaP. RNA-seq data were compared. Some 600 affymatrix PLUS2.0A chips and 1000 TCGA RNA-SEQ sequencing data were used to verify the data. On the basis of data comparison, the biological significance of the data was analyzed with Cytoscape software, GO, KEGG, Rectome and other databases. In order to understand prostate cancer and other tissue cancers The relationship between the disease and the specific expression of gene transcriptional regulatory networks and related biological pathways through systematic studies, thus further exploring the changes in genes specifically expressed in prostate cancer tissues and related biological characteristics, and explaining the molecular mechanisms of the development of prostate cancer. This study has important practical significance to further understand the molecular mechanism and diagnosis of the development of prostate cancer. Treatment provides useful basic research data.
[results]
1. the difference between the data of prostate cancer tissue and the data of the prostate cancer cell line is very different. There is no intersection of the WGCNA specific expression gene modules, which indicates that there is a great difference between the cell line and the sample of the prostatic clinical tissue.
2. the 388 specific genes were screened from the prostate cancer RNA-SEQ data published in the cellres article. 238 specific genes were screened from the prostate cancer RNA-SEQ data published in the article on PNAS, of which there were 8 genes in the intersection of two sets, that is, 8 genes were in metastatic prostate cancer. A stable expression.
3. using chip data, TCGA data, and GO and KEGG network analysis of all the specific expression results. We found that the PI3K/Akt/mTOR pathway plays a vital role in any prostate cancer data. It also found the TGF- beta /SMAD pathway, the functional pathway of the sticky polysaccharide, and the function of the extracellular structure. Pathways, Notch pathways, and some neurologic pathways occur simultaneously with the PI3K pathway.
【學(xué)位授予單位】：南昌大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R737.25

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