Zhang Peng, Zheng Pan, Liu Yang
Division of Immunotherapy, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, United States.
OncoImmune, Inc., Rockville, MD, United States.
Front Genet. 2019 Jun 12;10:560. doi: 10.3389/fgene.2019.00560. eCollection 2019.
is a glycosyl-phosphatidyl-inositol linked glycoprotein expressed in a broad range of cell types including cancer cells. Although it is overexpressed in nearly 70% of human cancers, copy number variation of the locus has not been reported for any cancer. Here, we analyzed the genomics, transcriptomics, and clinical data of 1082 breast cancer (BRCA) samples and other cancer samples from the clinically annotated genomic database, The Cancer Genome Atlas (TCGA). The GISTIC2 method was applied to stratify the copy number, and Cox regression was performed to compare hazard ratio (HR) of overexpression, amplification and other traditional prognosis features for overall survival (OS). Our data demonstrated that amplification strongly correlated with its mRNA overexpression as well as mutant, cancer proliferation and metastasis features. In particular, amplification was enriched in basal-like subtype samples and associated with poor clinical outcome. Surprisingly, based on the univariate Cox regression analysis, overexpression ( = 1.62, = 0.010) and copy number amplification ( = 1.79, = 0.022) was more relevant to OS than mutant, mutation counts, diagnosis age, and BRCA subtypes. And based on multivariate survival analysis, amplification remained the most significant and independent predictor for worse OS ( = 1.88, = 0.015).
是一种糖基磷脂酰肌醇连接糖蛋白，在包括癌细胞在内的多种细胞类型中表达。尽管它在近70%的人类癌症中过表达，但尚未有任何癌症报道该基因座的拷贝数变异。在此，我们分析了来自临床注释基因组数据库“癌症基因组图谱（TCGA）”的1082例乳腺癌（BRCA）样本及其他癌症样本的基因组学、转录组学和临床数据。应用GISTIC2方法对该基因的拷贝数进行分层，并进行Cox回归以比较该基因过表达、扩增及其他传统预后特征对总生存期（OS）的风险比（HR）。我们的数据表明，该基因扩增与其mRNA过表达以及该基因突变、癌症增殖和转移特征密切相关。特别是，该基因扩增在基底样亚型样本中富集，并与不良临床结果相关。令人惊讶的是，基于单变量Cox回归分析，该基因过表达（HR = 1.62，P = 0.010）和拷贝数扩增（HR = 1.79，P = 0.022）与总生存期的相关性比该基因突变、突变计数、诊断年龄和BRCA亚型更高。基于多变量生存分析，该基因扩增仍然是总生存期较差的最显著且独立的预测因素（HR = 1.88，P = 0.015）。
