ZMIZ1-AS1编码区体细胞拷贝数变异在实体肿瘤分布及对预后的影响

The distribution of somatic copy number variation of ZMIZ1-AS1 coding region in solid tumors and its effection on prognosis

目的探索ZMIZ1-AS1编码区体细胞拷贝数变异在原发肿瘤组织分布及在特定肿瘤预后监测中的作用,为相关肿瘤预防提供特异性标志物线索及依据。方法由The Cancer Genome Atlas(TCGA)数据库下载31类实质肿瘤患者数据,用R 3.4.2进行统计分析,采用χ^2检验及Fisher精确概率法分析ZMIZ1-AS1编码区体细胞拷贝数变异的分布差异,采用Kruskal-Wallis检验分析其对ZMIZ1-AS1与ZMIZ1表达的影响以及采用COX比例风险回归模型分析其对患者预后的影响。结果10547名患者原发肿瘤组织ZMIZ1-AS1编码区体细胞拷贝数缺失与增加在不同实质肿瘤间的分布差异有统计学意义(χ^2=3218.284,P<0.01);Kruskal-Wallis检验显示,ZMIZ1-AS1编码区拷贝数变异显著影响多数肿瘤中的ZMIZ1-AS1、ZMIZ1表达;COX回归分析结果显示,ZMIZ1-AS1编码区体细胞拷贝数缺失显著增加低分化胶质瘤(HR=11.06,95%CI:7.28~16.80)和间皮瘤(HR=4.04,95%CI:1.56~10.48)患者死亡风险。结论不同实质肿瘤其ZMIZ1-AS1编码区拷贝数变异分布存在差异,ZMIZ1-AS1编码区体细胞拷贝数缺失可作为低分化胶质瘤和间皮瘤预后监测的特异性生物标志物。

Objective To explore the distribution of somatic copy number variation(CNV)of ZMIZ1-AS1 coding region in solid tumors and effection on prognosis monitoring of special tumors,and to provide the clue and basis for specific biomarker of related tumors prevention.Methods The data of 31 solid tumors were downloaded from The Cancer Genome Atlas(TCGA)and analyzed by R 3.4.1.Theχ^2 and Fisher’s exact test were used to analyze the distribution difference of somatic CNV of ZMIZ1-AS1 in cancers.The effects of somatic CNV of ZMIZ1-AS1 on the expression of ZMIZ1-AS1 and ZMIZ1 were analyzed by Kruskal-Wallis test,while COX proportional risk regression was applied to analyze the effects on prognosis of patients.Results There were significant differences of somatic copy number loss or gain of ZMIZ1-AS1 in primary tumor tissues of different solid tumors among10547 tumor patients(P<0.01).Kruskal-Wallis test showed that somatic CNV of ZMIZ1-AS1 had the significant influence on the expression of ZMIZ1-AS1 and ZMIZ1 in most tumors.The survival analysis results showed that the somatic copy number loss of ZMIZ1-AS1 coding region enhanced significantly the death risk of brain lower grade glioma(HR=11.06,95%CI:7.28-16.80)and mesothelioma(HR=4.04,95%CI:1.56-10.48).Conclusion There was significant difference in the distribution of CNV in ZMIZ1-AS1 coding region for different solid tumors,the somatic copy number loss in ZMIZ1-AS1 coding region may serve as the special biomarker of prognosis monitoring for brain lower grade glioma and mesothelioma.