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Based On The RNA-Seq Analysis To Explore ACTN4Function In Lung Cancer With Brain Metastasis

Posted on:2016-01-02Degree:MasterType:Thesis
Country:ChinaCandidate:R J GaoFull Text:PDF
GTID:2284330467999941Subject:Surgery
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Objective:Lung cancer is one of common malignant tumors in our country,Come a longway local recurrence and metastasis are the poor prognosis of patients with lungcancer is the most serious cause.The brain is lung cancer is common way to transferpart of the body,various malignant tumors account for about45%~65%.In theprocess of malignant tumor in the event of a transfer,changes in the gene mutationspectrum.So the primary tumor and metastatic lesions related gene sequencing andanalysis to judge the prognosis of malignant tumors, to guide the selection oftreatment measures and the development of new treatments are very importantguiding significance.This study through normal tissue lung cancer and lung cancermetastasis to the lungs in the organization after the transcriptome RNA sequencinganalysis,find out the difference to be markedly genes,based on the analysis of genefunction and signal pathway construction of gene function relation network andsignaling pathways that control network,in order to investigate in the signalingpathway in lung cancer with brain metastasis in the key position of genes,and thento explore the potential mechanism of lung cancer with brain to turn.Methods:Extracting a normal lung tissue in patients with brain metastases from lungcancer lung cancer RNA in turn lung cancer with brain tissue, after the PCRamplification, respectively, based on high-throughput sequencing (Illumina)platform sequenced to them,then measured the transcriptome sequences can bedivided into30T group (organization of brain metastases from lung cancer),16Tgroup (lung metastasis group),16N group (normal lungtissue).To pass through the quality control in the three groups of original data andthe Mapping statistical analysis,Gene function signal path analysis construct gene relation network,construction of signaling pathways regulat-ing network,trendsanalysis of gene function,analysis trend signal path-way analysis,construct generegulatory network,to focus on in the signaling pathway in the key position of genes.Note:This study is the transcriptome sequences in group has won three on the basisof the original data.Results:(1)16N,16T,30Tgroup Quality scores more than20,the mapping accuracy isgreater than99%.(2)16N group mappringRates was0.75633756、16T group mappringRates was0.91953095、30T group mappringRates group was0.91953095.(3)ACTN4standardized RPKM value:16N group was6.358689346,16T group was6.358689346,30T group was116.6838456. ACTN4differences in group T30vsN16multiples (aFold Chan) is18.350298.(4)For0,1,2,3,4,5,6,7trend model diagram and thetrend of the corresponding figure. ACTN4trend in4models, according to course oftrend diagram4ACTN4in brain metastases from lung cancer tissues have obviousincrease trend.(5)Get clear trend trend of gene function and significant sign alingpathways,4trends significantly affect gene function in the model are mainlyconcentrated in mRNA transcription in translation;Significantly affect signalingpathway is mainly cell adhesion receptors, extracellular matrix related to twoimportant migration pathway.(6)To build the relationship between the significantPathway and signaling pathways that control network diagram. Constructs the celladhesion receptors, extracellular matrix between signal control.(7)Build generegulation network function.Build myosin structure, actin cytoskeleton organizationcytoskeleton organization gene function relationship between the three.(8)Geneinteractions between attributes, interaction relationship between input gene of nodesand network diagram. Found in the whole network:ANTC4downstream in small celllung cancer Focal Adhesion and ECM-receptor of the two signaling pathways.Conclusion:1.ACTN4brain metastatic tumor with high expression in lung cancer, lungcancer and tissue adjacent to carcinoma in the expression difference is notobvious;trend chart and during the course of the late expression significantly raised,ShowACTN4and lung cancer is closely related to poor prognosis.2.ACTN4encoded protein actin4a-auxiliary with small cell lung cancer inFocal Adhesion (stick) and ECM-receptor (extracellular matrix) receptors signalingpathways are closely related,by adjusting the actin cytoskeleton organization,Bring onthe reorganization of cytoskeleton organization deformation and (or) affect cancer cellinvasion force.3.ACTN4may regulate cancer cell invasion force, directly or indirectlycontributed to the occurrence of lung cancer with brain metastasis.
Keywords/Search Tags:Lung cancer with brain metastasis, RNA sequencing, RNA-seq analysis ofdata, ACTN4
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