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Study Specific Expression Of Factor In Prostate Cancer Through WGCNA

Posted on:2015-05-08Degree:MasterType:Thesis
Country:ChinaCandidate:K F HuangFull Text:PDF
GTID:2284330422977968Subject:Genetics
Abstract/Summary:PDF Full Text Request
Prostate cancer is now the world’s second most common cancer in men, while theannual incidence rate showed an increasing trend. All men have a risk of prostatecancer, about1/6of the men in their life, may be diagnosed with prostate cancer, Inthose,1/36people will die from prostate cancer. Although Asian men, especiallyChinese men, relative to the incidence is much lower for men in Europe and America,but in recent years the incidence of prostate cancer in Chinese men increasingly highincidence of prostate cancer in genitourinary malignancies have been from the firstthree ranked as the first, has become an important disease of older men endanger lifeand health.With the rapid development of molecular biology, especially in large-scalesequencing data generated, most tumor occurrence and development, changes in thecellular and molecular level, people have a better understanding. Prostate cancer is avery complex cancer development process which occur there are a variety of factors,many genes interact. The expression changes of PI3K/AKT/MTOR way, WNTpathway, TGF-β/SMAD pathway may be able to enhance tumor cell growth,metastasis and invasion, and PI3K/AKT/MTOR particular way have a very importantrole in prostate cancer. However, for the design development process mechanism ofprostate cancer, scientists is still very superficial understanding. Therefore, the studyof the similarities and differences between prostate cancer and other cancers, canprovide important genetic level as a basis for the development of prostate cancer.we also need to note that the early diagnosis of prostate cancer has importantclinical implications in the treatment of prostate cancer. Currently, PSA (prostatespecific antigen) is an important marker for the detection of prostate cancer. However,PSA is not cancer-specific, the incidence of prostatitis can also cause PSA testingpositive. Therefore, we need an effective target molecules from screening for prostatecancer.After microarray, high-throughput sequencing technology to generate, detect tensof thousands of genes can be expressed in one-time spectrum, the traditional methodsof analysis of individual genes are no longer applicable. With more and more data isgenerated, the bioinformatics analysis method put forward higher requirements, weneed to integrate vast amounts of data, analysis, screened out the appropriate genes,and reveal a possible link between these genes and biological functions. Therefore, this study used a high-throughput sequencing, microarray chipapproach that combines WGCNA co-expression network analysis, GO, KEGGbiological functions such as database, trying to provide some ideas for prostate cancerresearch in the future.【purpose】In this study, we do bioinformatics analysis to prostate cancer data from twoliterature respectively in GEO(Gene Expression Omnibus),and other four cancertissues data in GEO by WGCNA(Weighted Gene Co-expression Network Analysis)in Bioconductor of R language. These data include40prostate cancer RNA-seq data(Gleason score>6),20prostate cancer adjacent tissue RNA-seq data (normal), and16lung RNA-seq data, three hepatocellular carcinoma and three corresponding tissueRNA-seq data,10acute leukemia RNA-seq data,5papillary renal cell RNA-seq data,and then use the five kinds of commonly used prostate cancer cell lines: PrEC, PWRE,DU145, LNCaP, VCaP of RNA-seq data for comparison. And the use of about600affymatrix PLUS2.0A chip data, and1000TCGA RNA-SEQ sequencing datavalidation. Basing on the comparison of data, the biological significance of the datain-depth analysis have been done by using cytoscape software, and GO, KEGG,rectome databases.In order to understand the similarities and differences betweenprostate cancer and other cancer tissue, to further investigate the changes in prostatecancer tissue-specific expression of genes and their biological characteristics, weintensive study the transcriptional gene regulatory networks, as well as theirbiological pathways involved in specific systems, describing the development ofprostate cancer. The study has important practical significance, and hopes to use anexisting database, to use the biological means of information, to find biomarkers forprostate cancer-specific expression and to explore the molecular mechanisms ofprostate cancer differs from other cancer development. This study provides a usefulbasis for research data to further understand the molecular mechanisms and thedevelopment of prostate cancer diagnosis and treatment.【result】1. The results of the prostate cancer cell lines is very different from prostatecancer tissue. There is no specific gene expression modules in intersection,indicating there is a big difference between the prostate cell lines and clinicaltissue samples 2. The prostate cancer RNA-SEQ data from published articles on CellRes screenout388specific genes. The prostate cancer RNA-SEQ data from publishedarticles on PNAS screen out238specific genes. The intersection of the twosets include eight genes, i.e., there are8metastatic prostate cancer geneexpressing stably.3. Using microarray data, TCGA data for validation. All results expressingspecifically have been done GO and KEGG network analysis. We found that,regardless of any prostate cancer data, PI3K/Akt/mTOR pathway plays acrucial role. Its also found TGF-β/SMAD way, mucopolysaccharidesfunctional pathways, extracellular tissue functional pathways, NOTCHpathway, some of the neurological pathways occur simultaneously withPI3K pathways...
Keywords/Search Tags:prostate cancer, transcriptome sequencing, gene chips, coexpressionnetwork analysis
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