乳腺癌中跨膜蛋白81基因高表达不利于患者预后
High expression of transmembrane protein 81 is bad for prognosis of breast cancer patients
目的 揭示乳腺癌组织中跨膜蛋白81（TMEM81）的表达变化及其与预后的关系。 方法 使用TCGA数据库的门户网站cBioPortal、UALCAN以及癌症多组学和临床数据库LinkedOmics分析TMEM81在乳腺癌组织中的变化及其与临床预后的关系。 结果 cBioPortal分析结果显示26%乳腺癌患者癌组织中TMEM81基因发生了改变，包括突变、拷贝数畸变和mRNA水平上调， mRNA水平上调超过默认阈值（EXP≥2）的比例为18%，且TMEM81 mRNA水平上调不利于患者预后（P<0.05）；UALCAN分析结果显示乳腺癌组织中TMEM81 mRNA水平显著高于正常组织（P<0.01）；LinkedOmics分析结果显示癌组织TMEM81 mRNA水平分别受到乳腺癌PAM50分型、雌激素受体、孕激素受体、病理分期、病理T分期、组织学类型、种族和年龄的影响（P<0.01, P<0.01，P<0.01，P<0.01，P<0.01，P<0.01，P<0.01，P<0.05）。最后， TMEM81 mRNA水平与其基因拷贝数畸变正相关（P<0.01），而与其DNA甲基化水平负相关（P<0.01）。 结论 乳腺癌组织中TMEM81基因拷贝数增加和甲基化水平降低促进其表达，TMEM81高表达不利于预后，可作为乳腺癌预后的候选标志物。
Objective To investigate the expression of transmembrane protein 81 (TMEM81) in breast cancer and its correlation with the prognosis of breast cancer. Methods The cBioPortal, UALCAN, and the cancer multi-omics and clinical database LinkedOmics were used to analyze changes of TMEM81 gene in breast cancer and its relationship with clinical prognosis. Results Analysis by cBioPortal showed that TMEM81 gene was changed in 26% invasive breast cancer patients including mutation, copy number alteration and mRNA up-regulation, in which 18% patients’ TMEM81 mRNA level was higher than default threshold (EXP≥2). Besides, up-regulation of TMEM81 mRNA was bad for prognosis (P<0.05). Results From UALCAN showed that level of TMEM81 mRNA increased significantly in invasive breast cancer tissues compared with normal breast tissues (P<0.01). Results from LinkedOmics showed that TMEM81 expression was significantly affected by PAM50, ER, PR, pathologic stage, pathology T stage, histological type, race and age respectively (P<0.01, P<0.01, P<0.01, P<0.01,P<0.01, P<0.05, P<0.01, P<0.05). TMEM81 mRNA level was positively correlated with its gene copy-number alteration (P<0.01), and was negatively correlated with its DNA methylation (P<0.01). Conclusion The alteration of gene copy number and the level of DNA methylation promote the expression of TMEM81 , the higher level of its mRNA is, the worse it is for prognosis, beyond that TMEM81 could become a candidate marker for prognosis of breast cancer.
乳腺癌 / 跨膜蛋白81 / 预后 / 拷贝数畸变 / DNA甲基化
Breast cancer / Transmembrane Protein 81; Prognosis; Copy number alteration; DNA methylation
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江苏医药职业学院科技创新团队建设计划（2018）；江苏省“青蓝工程”项目（2016）；盐城市医学科技发展计划项目（YK2017050）
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