肿瘤纯度——肿瘤研究中一个被忽视的潜在混杂因素
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摘要
肿瘤组织中除了肿瘤细胞之外还有免疫细胞、基质细胞、间质细胞等非肿瘤细胞,共同影响肿瘤发生发展。肿瘤纯度与肿瘤患者临床特征、基因组表达和生物学特性显著相关,研究过程中对肿瘤样本进行分析时应充分考虑肿瘤纯度的影响。本文主要从概念、现有的计算方式及对基因组分析的影响三个方面对肿瘤纯度行简要综述。
Tumor tissues are often composed of not only tumor cells but also non-tumor cells such as immune cells, stromal cells and mesenchymal cells. They play an important role in tumor growth and progress together. Tumor purity is significantly associated with clinical features, gene expression and tumor biology,indicating that we need to fully consider the potential confounding effect of tumor purity on tumor analyses.This article reviews the concept, calculate methods and impact of tumor purity on genomic analysis.
Tumor tissues are often composed of not only tumor cells but also non-tumor cells such as immune cells, stromal cells and mesenchymal cells. They play an important role in tumor growth and progress together. Tumor purity is significantly associated with clinical features, gene expression and tumor biology,indicating that we need to fully consider the potential confounding effect of tumor purity on tumor analyses.This article reviews the concept, calculate methods and impact of tumor purity on genomic analysis.
引文
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[2]Sacher AG,Gandhi L.Biomarkers for the Clinical Use of PD-1/PD-L1 Inhibitors in Non-Small-Cell Lung Cancer:A Review[J].JAMA Oncol,2016,2(9):1217.
[3]Yarchoan M,Hopkins A,Jaffee EM.Tumor Mutational Burden and Response Rate to PD-1 Inhibition[J].N Engl J Med,2017,377(25):2500-1.
[4]Baretti M,Le DT.DNA Mismatch Repair in Cancer[J].Pharmacol Ther,2018,189:45-62.
[5]Meng X,Huang Z,Teng F,et al.Predictive biomarkers in PD-1/PD-L1 checkpoint blockade immunotherapy[J].Cancer Treat Rev,2015,41(10):868-76.
[6]Tang H,Qiao J,Fu Y X.Immunotherapy and tumor microenvironment[J].Cancer Lett,2016,370(1):85-90.
[7]Zou W,Wolchok JD,Chen L.PD-L1(B7-H1)and PD-1 pathway blockade for cancer therapy:Mechanisms,response biomarkers,and combinations[J].Sci Transl Med,2016,8(328):328rv4.
[8]Aran D,Sirota M,Butte AJ.Systematic pan-cancer analysis of tumour purity[J].Nat Commun,2015,6:8971.
[9]Junttila MR,de Sauvage FJ.Influence of tumour microenvironment heterogeneity on therapeutic response[J].Nature,2013,501(7467):346-54.
[10]Pagès F,Galon J,Dieu-Nosjean MC,et al.Immune infiltration in human tumors:a prognostic factor that should not be ignored[J].Oncogene,2010,29(8):1093-102.
[11]Rhee JK,Jung YC,Kim KR,et al.Impact of tumor purity on immune gene expression and clustering analyses across multiple cancer types[J].Cancer Immunol Res,2018,6(1):87-97.
[12]Zhu W,Kuziora M,Creasy T,et al.BubbleTree:an intuitive visualization to elucidate tumoral aneuploidy and clonality using next generation sequencing data[J].Nucleic Acids Res,2016,44(4):e38.
[13]Carter SL,Cibulskis K,Helman E,et al.Absolute quantification of somatic DNA alterations in human cancer[J].Nat Biotechnol,2012,30(5):413-21.
[14]Zheng X,Zhao Q,Wu HJ,et al.MethylPurify:tumor purity deconvolution and differential methylation detection from single tumor DNA methylomes[J].Genome Biol,2014,15(8):419.
[15]Yoshihara K,Shahmoradgoli M,Martínez E,et al.Inferring tumour purity and stromal and immune cell admixture from expression data[J].Nat Commun,2013,4:2612.
[16]Zhang N,Wu HJ,Zhang W,et al.Predicting tumor purity from methylation microarray data[J].Bioinformatics,2015,31(21):3401-5.
[17]Zheng X,Zhang N,Wu HJ,et al.Estimating and accounting for tumor purity in the analysis of DNA methylation data from cancer studies[J].Genome Biol,2017,18(1):17.
[18]Dou H,Fang Y,Zheng X.Universal informative CpG sites for inferring tumor purity from DNA methylation microarray data[J].J Bioinform Comput Biol,2018,16(30):1750030.
[19]Bao L,Pu M,Messer K.AbsCN-seq:a statistical method to estimate tumor purity,ploidy and absolute copy numbers from next-generation sequencing data[J].Bioinformatics,2014,30(8):1056-63.
[20]Benelli M,Romagnoli D,Demichelis F.Tumor purity quantification by clonal DNA methylation signatures[J].Bioinformatics,2018,34(10):1642-9.
[21]Favero F,Joshi T,Marquard AM,et al.Sequenza:allele-specific copy number and mutation profiles from tumor sequencing data[J].Ann Oncol,2015,26(1):64-70.
[22]Zhang W,Feng H,Wu H,et al.Accounting for tumor purity improves cancer subtype classification from DNA methylation data[J].Bioinformatics,2017,33(17):2651-7.
[23]Zhang W,Long H,He B,et al.DECtp:Calling Differential Gene Expression Between Cancer and Normal Samples by Integrating Tumor Purity Information[J].Front Genet,2018,9:321.
[24]Geeleher P,Nath A,Wang F,et al.Cancer expression quantitative trait loci(eQTLs)can be determined from heterogeneous tumor gene expression data by modeling variation in tumor purity[J].Genome Biol,2018,19(1):130.
[25]Zhang C,Cheng W,Ren X,et al.Tumor Purity As an Underlying Key Factor in Glioma[J].Clin Cancer Res,2017,23(20):6279-91.
[26]Mao Y,Feng Q,Zheng P,et al.Low tumor purity is associated with poor prognosis,heavy mutation burden,and intense immune phenotype in colon cancer[J].Cancer Manag Res,2018,10:3569-77.
[27]Rooney MS,Shukla SA,Wu CJ,et al.Article:Molecular and Genetic Properties of Tumors Associated with Local Immune Cytolytic Activity[J].Cell,2015,160(1-2):48-61.
[28]Elloumi F,Hu Z,Li Y,et al.Systematic Bias in Genomic Classification Due to Contaminating Non-neoplastic Tissue in Breast Tumor Samples[J].BMC Med Genomics,2011,4:54.
[29]Isella C,Terrasi A,Bellomo SE,et al.Stromal contribution to the colorectal cancer transcriptome[J].Nat Genet,2015,47(4):312-9.
[30]Moffitt RA,Marayati R,Flate EL,et al.Virtual microdissection identifies distinct tumor-and stroma-specific subtypes of pancreatic ductal adenocarcinoma[J].Nat Genet,2015,47(10):1168-78.