要.Angiogenesisisoneofthehallmarksofcancer.Wehypothesizedthatintra-tumoralangiogenesiscorrelateswithinflammationandmetastasisinbreastcancerpatients.Totestthishypothesis,wegeneratedanangiogenesispathwayscoreusinggenesetvariationanalysisandanalyzedthetumortranscriptomeofbreastcancerpatientsfromTheCancerGenomeAtlasBreastCancer(TCGA-BRCA),MolecularTaxonomyofBreastCancerInternationalConsortium(METABRIC),GSE,GSE,GSE,andGSEcohorts.Wefoundthatthescorecorrelatedwithexpressionofvariousangiogenesis-,vascularstability-,andsphingosine-1-phosphate(S1P)-relatedgenes.Surprisingly,theangiogenesisscorewasnotassociatedwithbreastcancersubtype,Nottinghampathologicalgrade,clinicalstage,responsetoneoadjuvantchemotherapy,orpatientsurvival.However,ahighscorewasassociatedwithalowfractionofbothfavorableandunfavorableimmunecellinfiltrationsexceptfordendriticcellandM2macrophage,andwithLeukocyteFraction,TumorInfiltratingLymphocyteRegionalFractionandLymphocyteInfiltrationSignaturescores.High-scoretumorshadsignificantenrichmentforunfavorableinflammation-relatedgenesets(interleukin(IL)6,andtumornecrosisfactor(TNF)α-andTGFβ-signaling),aswellasmetastasis-relatedgenesets(epithelialmesenchymaltransition,andHedgehog-,Notch-,andWNT-signaling).Highscorewassignificantlyassociatedwithmetastaticrecurrenceparticularlytobrainandbone.Inconclusion,usingtheangiogenesispathwayscore,wefoundthatintra-tumoralangiogenesisisassociatedwithimmunereaction,inflammationandmetastasis-relatedpathways,andmetastaticrecurrenceinbreastcancer.血管生成是癌症的标志之一。我们猜想肿瘤内血管生成与乳腺癌患者的炎症和转移相关。为了验证这一假设，我们使用基因集变异分析生成了血管生成通路评分，并分析了名乳腺癌患者的肿瘤转录组信息，这些患者来自TCGA-BRCA、METABRIC、GSE、GSE、GSE和GSE队列。我们发现评分与各种血管生成、血管稳定性和S1P相关基因的表达有关。血管生成评分与乳腺癌亚型、病理分级、临床分期、对新辅助化疗的反应或患者生存期无关。然而，高分值与除树突状细胞和M2巨噬细胞外的有利和不利免疫细胞浸润的低比例相关，与白细胞比例、肿瘤浸润性淋巴细胞比例和淋巴细胞浸润签名分数相关。(2)高分值与除树突状细胞和M2巨噬细胞外，其他免疫细胞浸润有利和不利的比例较低，与白细胞分数、肿瘤浸润淋巴细胞区域分数和淋巴细胞浸润Signature分数有关。得分高的肿瘤明显富含不良炎症相关基因集(白细胞介素6、肿瘤坏死因子α和转化生长因子β信号通路)，以及转移相关基因集(上皮间质转化、Hedgehog、Notch和Wnt信号通路)。高分值与转移性复发显著相关，特别是脑和骨的转移性复发。综上所述，利用血管生成通路评分，我们发现肿瘤内血管生成与免疫反应、炎症和转移相关途径以及乳腺癌的转移复发有关。
文献来源：IntJMolSciSep13;(18)
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