Amplification of the CD24 Gene Is an Independent Predictor for Poor Prognosis of Breast Cancer
Amplification of the CD24 Gene Is an Independent Predictor for Poor Prognosis of Breast Cancer
复制标题
DOI：
10.3389/fgene.2019.00560
复制
发表时间：
2019-06-12
影响因子：
3.7
通讯作者：
Liu, Yang
中科院分区：
文献类型：
--
作者：
Zhang, Peng;Zheng, Pan;Liu, Yang
CD 24是糖基-磷脂酰-肌醇连接的糖蛋白，在包括癌细胞在内的广泛细胞类型中表达。虽然它在近70%的人类癌症中过表达，但CD 24基因座的拷贝数变异在任何癌症中都没有报道。在这里，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）样本和其他癌症样本的基因组学，转录组学和临床数据。采用GISTIC 2方法对CD 24拷贝数进行分层，并进行考克斯回归分析，比较CD 24过表达、扩增和其他传统预后特征对总生存期（OS）的危险比（HR）。我们的数据表明，CD 24扩增与其mRNA过表达以及TP 53突变，肿瘤增殖和转移特征密切相关。特别是，CD 24扩增在基底细胞样亚型样本中富集，并与不良临床结局相关。令人惊讶的是，基于单变量考克斯回归分析，CD 24过表达（HR = 1.62，P = 0.010）和拷贝数扩增（HR = 1.79，P = 0.022）与OS的相关性高于TP 53突变、突变计数、诊断年龄和BRCA亚型。多因素生存分析结果显示，CD 24扩增仍是OS恶化的独立预测因子（HR = 1.88，P = 0.015）。
CD24 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 CD24 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 CD24 copy number, and Cox regression was performed to compare hazard ratio (HR) of CD24 overexpression, amplification and other traditional prognosis features for overall survival (OS). Our data demonstrated that CD24 amplification strongly correlated with its mRNA overexpression as well as TP53 mutant, cancer proliferation and metastasis features. In particular, CD24 amplification was enriched in basal-like subtype samples and associated with poor clinical outcome. Surprisingly, based on the univariate Cox regression analysis, CD24 overexpression (HR = 1.62, P = 0.010) and copy number amplification (HR = 1.79, P = 0.022) was more relevant to OS than TP53 mutant, mutation counts, diagnosis age, and BRCA subtypes. And based on multivariate survival analysis, CD24 amplification remained the most significant and independent predictor for worse OS (HR = 1.88, P = 0.015).