基于高通量多组学数据分析ESYT3在乳腺癌中的表达及临床意义

Analysis of ESYT3 expression and its clinical significance in breast cancer based on high-throughput multi-omics databases

目的基于高通量数据库分析扩展突触结合蛋白3(ESYT3)在乳腺癌中的表达及临床意义。方法使用TCGA数据库和基因表达数据库(GEO)的门户网站(c Bio Portal和Oncomine)以及癌症多组学和临床数据库Linked Omics分析ESYT3在乳腺癌中的变化及其与临床预后的关系;分别采用Kaplan-Meier法分析ESYT3变异与乳腺癌患者生存之间的关系,非参数检验分析正常乳腺组织和浸润性乳腺癌组织中ESYT3的表达差异,Spearman非参数检验分析浸润性乳腺癌中ESYT3 m RNA水平与临床各指标的相关性以及基因拷贝数变化和甲基化水平对m RNA表达的影响。结果 c Bio Portal分析结果显示1 098例浸润性乳腺癌患者中,122例发生了ESYT3 m RNA的改变(包括突变、拷贝数变化和m RNA水平上调),其中,ESYT3 m RNA水平上调超过默认阈值(EXP≥2)的占10%,且不利于患者预后(P<0.05);Oncomine分析结果显示,浸润性乳腺癌组织中ESYT3m RNA水平明显高于癌旁组织(P<0.01);Linked Omics分析结果显示,浸润性乳腺癌中ESYT3 m RNA水平分别受雌激素受体、孕激素受体、PAM50分型、组织学类型、年龄以及肿瘤纯度的影响(P<0.01);ESYT3 m RNA水平与其基因拷贝数呈正相关(P<0.01),而与其DNA甲基化呈负相关(P<0.01)。结论 ESYT3拷贝数增加和低甲基化促进其表达,且ESYT3高表达不利于乳腺癌患者预后,可作为预后的候选标志物。

Objective To analyze the expression and prognostic significance of extended synaptotagmins-3 （ESYT3） in breast cancer based on high-throughput multi-omics databases. Methods The cBioPortal and Oncomine of TCGA （The Cancer Genome Atlas） data- base and gene expression database （GEO） , as well as the cancer multi-omics and clinical database LinkedOmics were used to analyze the changes of ESYT3 gene in breast cancer and its relationship with the parameters of clinical prognosis of patients. Kaplan-Meier method was used to analyze the relationship between the mutation of ESYT3 gene and the survival of breast cancer patients. Non-para- metric test was used to analyze the expression values of ESYT3 in normal breast and invasive breast cancer tissues. Nonparametric Spearman test was used to analyze the correlation between ESYT3 mRNA levels in invasive breast cancer and clinical parametors, as well as the effects of changes of both gene copy number and methylation level on ESYT3 mRNA expression. Results The results of cBioPortal showed that the changes of ESYT3 mRNA presented in 122 cases of 1 098 patients with invasive breast cancer, including mutation, alteration of copy number and up-regulated mRNA level. Among them, poor prognosis was predicted in 10 percent of patients in whom ESYT3 mRNA levels were higher than defauh threshold （ EXP ≥ 2 ） （ P〈 0.05 ）. The resuhs from Oncomine showed ESYT3 mRNA levels in mammary duct carcinoma were significantly higher than those in the tissue adjacent to breast cancer （P〈0.01）. The re- suits from LinkedOmics showed that ESYT3 mRNA level was significantly affected by estrogen receptor, rogestrone receptor, PAM50 type, histological type, age and tumor purity （P〈0.01）. The mRNA level of ESYT3 was positively correlated with its gene copy-number alteration （P〈0.01）, but negatively correlated with its DNA methylation （P〈0.01）. Conclusion Increased copy-number and hypom- ethylation of ESYT3 gene may promote its expression. High expression of ESYT3 predict poor prognosis of breast cancer patients as a candidate biomarker.