中文摘要、結(jié)論在本研究中，通過一系列的生物信息學分析揭示了卵巢癌的外泌體相關(guān)特征并最終構(gòu)建了預后預測模型。首先，為揭示卵巢癌的細胞組成情況，利用scRNA-seq數(shù)據(jù)，通過質(zhì)控，降維聚類，共注釋出7種細胞類型。通過分析不同樣本中細胞類型占比，發(fā)現(xiàn)上皮細胞在組織中顯著富集。還利用scRNA-seq與ST-seq數(shù)據(jù)結(jié)合，將注釋好的scRNA-seq數(shù)據(jù)映射到ST-seq數(shù)據(jù)上，構(gòu)建了卵巢癌的細胞圖譜。其次，通過inferCNV分析，推斷出了上皮細胞中的惡性細胞。基于流行的三種算法對ERG進行了scRNA-seq和ST-seq數(shù)據(jù)的富集評分并取均值作為最終的ERS。結(jié)果表明，惡性細胞與單核/巨噬細胞具有較高的ERS。并且通過對不同ERS評分惡性細胞進行差異分析和KEGG富集分析，揭示了惡性細胞中外泌體相關(guān)的氧化磷酸化（OXPHOS）代謝通路。接下來，基于偽時間軌跡分析，揭示了惡性細胞發(fā)育過程中ERG表達呈現(xiàn)上調(diào)趨勢，并獲取在惡性細胞發(fā)育過程中顯著變化的基因?；诩毎g通訊分析，剖析了不同細胞間的通訊模式，結(jié)果表明單核/巨噬細胞與高低ERS兩組惡性細胞在癌癥的PD-L1表達和PD-1檢查點通路上的富集存在差異。并深入挖掘了單核/巨噬細胞與惡性細胞間的L-R-TF，通過對TF調(diào)控的靶基因進行富集分析，揭示其所參與的與細胞增殖、腫瘤生長相關(guān)的信號通路。最后，基于前期所獲得的三個基因集構(gòu)建了PPI網(wǎng)絡。通過衡量了網(wǎng)絡中每個節(jié)點的點度中心性、中介中心性以及PCI，鑒定出其中的關(guān)鍵基因。隨后，通過三種經(jīng)典回歸分析方法，識別出5個與卵巢癌患者生存顯著相關(guān)的基因，并利用TCGA數(shù)據(jù)庫中卵巢癌患者bulkRNA-seq數(shù)據(jù)構(gòu)建了預后預測模型。綜上所述，本研究構(gòu)建了卵巢癌的細胞圖譜，揭示卵巢癌外泌體的相關(guān)特征；基于不同ERS惡性細胞間的差異，揭示了惡性細胞外泌體相關(guān)的OXPHOS代謝通路；并剖析了高低ERS兩組惡性細胞的動態(tài)變化及細胞通訊模式；通過上述一系列生物學分析，最終篩選出與卵巢癌患者OS呈現(xiàn)顯著相關(guān)的5個基因，更開發(fā)出了具有臨床決策支持價值的工具，為推進卵巢癌的精準醫(yī)療策略提供了新的生物標志物及理論依據(jù)。參考文獻ADDINEN.REFLIST1. 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8、附錄附表1外泌體基因集SupplementaryTable1ExosomegenesetGenesymbleEnsembleChromosome/scaffoldnameGenestart(bp)Geneend(bp)StrandCDC42ENSG00000070831122052627220929461CPENSG000000474573149162410149222055-1CD47ENSG000001967763108043094108091862-1EEF1A1ENSG0000015650867351575073523797-1EPCAMENSG00000119888247345158473876011ERBB2ENSG000001417361739687914397304261FGFR2ENSG0000006646810121478334121598458-1CHEK2ENSG00000183765222868774328742422-1BARD1ENSG000001383762214725646214809711-1TSC2ENSG0000010319716204746520894871CASP7ENSG00000165806101136791621137309071SFNENSG00000175793126863138268644571TYRENSG000000774981189177452892957591CCKBRENSG0000011014811625973662721271CYP11A1ENSG00000140459157433775974367740-1GATA4ENSG00000136574811676959117600021ABCB11ENSG000000737342168922938169031322-1IVLENSG0000016320711529085451529118861BIDENSG00000015475221773413817774770-1SDHAENSG0000007357852182412570821USF1ENSG000001587731161039251161045977-1RHOENSG0000016391431295286401295351691TAC1ENSG00000006128797731908977404721HLA-DQA1ENSG00000196735632628179326470621RIPK1ENSG000001372756306399131151871CUL4AENSG00000139842131132081931132671081ABCB5ENSG00000004846720615207207770381ADCYAP1ENSG00000141433189049439121721FZD5ENSG000001632512207762586207769563-1RANBP1ENSG000000999012220115938201273571CASC3ENSG000001083491740140318401721711GPBAR1ENSG0000017992122182594962182638591PSMC5ENSG000000871911763827152638320261POLR2KENSG0000014766981001505841001540021續(xù)附表1外泌體基因集GenesymbleEnsembleChromosome/scaffoldnameGenestart(bp)Geneend(bp)StrandPLCB4ENSG0000010133320906876394812421DOK1ENSG00000115325274549026745575541SF3B4ENSG000001433681149923317149928344-1GTF2IENSG00000263001774657667747606921NOC2LENSG000001889761944204959309-1MEF2AENSG000000683051599565417997164661CYC1ENSG0000017909181440950271440975251MRPL21ENSG00000197345116889127668903835-1MRPL4ENSG000001053641910251901102600451BDKRB2ENSG000001683981496204679962441661PIK3R5ENSG000001415061788789118965712-1PRPF3ENSG0000011736011503214761503531951PSMD2ENSG0000017516631842987091843090541SNRPA1ENSG0000013187615101281510101295282-1RPS10ENSG0000012461463441745434426125-1ADRA1BENSG0000017021451598650801599725441TRIOBPENSG000001001062237696988377765561RPL26L1ENSG0000003724151729587291729697711FAM162AENSG0000011402331223841761224123341SF3A2ENSG0000010489719223650422486791HER2ENSG000001417361739687914397304261CD82ENSG000000851171144564427446203581CD24ENSG000002723986106969831106975627-1Del-1ENSG0000016417658394055484384793-1DicerENSG00000100697149508622895158010-1POSTNENSG00000133110133756258337598844-1FGFR3ENSG000000680784179329318088721FIBPENSG00000172500116588374165888539-1FRS2ENSG000001662251269470349695797891FTH1ENSG00000167996116195971861967660-1FTLENSG000000870861948965301489668781GSTP1ENSG000000842071167583595675866561HOXC6ENSG000001977571253990624540308231HTR7ENSG00000148680109074082390857698-1IGF1RENSG000001404431598648971989645301IL1RAPENSG0000019608331905140511906597501ITGB1ENSG00000150093103290031933005792-1續(xù)附表1外泌體基因集GenesymbleEnsembleChromosome/scaffoldnameGenestart(bp)Geneend(bp)StrandKISS1RENSG00000116014199172879210151KRT14ENSG00000186847174158227941586921-1LDHAENSG000001343331118394388184084251MTDHENSG00000147649897644179977287701NANOGENSG0000011170412778779477991411NEUROD1ENSG000001629922181673088181680876-1PlauENSG000001228611073909177739174971RAB13ENSG000001435451153981617153986358-1RPL28ENSG000001081071955385345554032501S1PR2ENSG00000267534191022143310231331-1TGFBR1ENSG00000106799999104038991541921TRPC5ENSG00000072315X111774315112082776-1TSG101ENSG00000074319111846833618527232-1UCHL1ENSG