Abstract：
BACKGROUND: Triple negative breast cancer (TNBC) is a heterogeneous group of tumors with early relapse, poor overall survival, and lack of effective treatments. Hence, new prognostic biomarkers and therapeutic targets are needed.
METHODS: The expression profile of all twenty-five human selenoproteins was analyzed in TNBC by a systematic approach.In silicoanalysis was performed on publicly available mRNA expression datasets (Cancer Cell Line Encyclopedia, CCLE and Library of Integrated Network-based Cellular Signatures, LINCS). Reverse transcription quantitative PCR analysis evaluated selenoprotein mRNA expression in TNBC versus non-TNBC and normal breast cells, and in TNBC tissues versus normal counterparts. Immunohistochemistry was employed to study selenoproteins in TNBC tissues. STRING and Cytoscape tools were used for functional and network analysis.
RESULTS: GPX1, GPX4, SELENOS, TXNRD1 and TXNRD3 were specifically overexpressed in TNBC cells, tissues and CCLE/LINCS datasets. Network analysis demonstrated that SELENOS-binding valosin-containing protein (VCP/p97) played a critical hub role in the TNBCselenoproteins sub-network, being directly associated with SELENOS expression. The combined overexpression of SELENOS and VCP/p97 correlated with advanced stages and poor prognosis in TNBC tissues and the TCGA dataset.
CONCLUSIONS: Combined evaluation of SELENOS and VCP/p97 might represent a novel potential prognostic signature and a therapeutic target to be exploited in TNBC.
METHODS: The expression profile of all twenty-five human selenoproteins was analyzed in TNBC by a systematic approach.In silicoanalysis was performed on publicly available mRNA expression datasets (Cancer Cell Line Encyclopedia, CCLE and Library of Integrated Network-based Cellular Signatures, LINCS). Reverse transcription quantitative PCR analysis evaluated selenoprotein mRNA expression in TNBC versus non-TNBC and normal breast cells, and in TNBC tissues versus normal counterparts. Immunohistochemistry was employed to study selenoproteins in TNBC tissues. STRING and Cytoscape tools were used for functional and network analysis.
RESULTS: GPX1, GPX4, SELENOS, TXNRD1 and TXNRD3 were specifically overexpressed in TNBC cells, tissues and CCLE/LINCS datasets. Network analysis demonstrated that SELENOS-binding valosin-containing protein (VCP/p97) played a critical hub role in the TNBCselenoproteins sub-network, being directly associated with SELENOS expression. The combined overexpression of SELENOS and VCP/p97 correlated with advanced stages and poor prognosis in TNBC tissues and the TCGA dataset.
CONCLUSIONS: Combined evaluation of SELENOS and VCP/p97 might represent a novel potential prognostic signature and a therapeutic target to be exploited in TNBC.
摘要：
背景：三阴性乳腺癌（TNBC）是一类具有早期复发的异质性肿瘤，总体生存率低，缺乏有效的治疗方法。因此，需要新的预后生物标志物和治疗靶点.
方法:通过系统方法在TNBC中分析所有25种人硒蛋白的表达谱。在公开可用的mRNA表达数据集上进行了硅分析(癌细胞系百科全书，CCLE和基于网络的集成蜂窝签名库，LINCS）。逆转录定量PCR分析评估了TNBC与非TNBC和正常乳腺细胞中硒蛋白mRNA的表达，在TNBC组织与正常组织中。免疫组织化学用于研究TNBC组织中的硒蛋白。STRING和Cytoscape工具用于功能和网络分析。
结果：GPX1，GPX4，SELENOS，TXNRD1和TXNRD3在TNBC细胞中特异性过表达，组织和CCLE/LINCS数据集。网络分析表明，SELENOS结合含有效球蛋白的蛋白（VCP/p97）在TNBC硒蛋白亚网络中起着关键的枢纽作用，与SELENOS表达直接相关。SELENOS和VCP/p97的联合过表达与TNBC组织和TCGA数据集中的晚期和不良预后相关。
结论：联合评估SELENOS和VCP/p97可能代表了一种新的潜在预后特征和TNBC的治疗靶点。
方法:通过系统方法在TNBC中分析所有25种人硒蛋白的表达谱。在公开可用的mRNA表达数据集上进行了硅分析(癌细胞系百科全书，CCLE和基于网络的集成蜂窝签名库，LINCS）。逆转录定量PCR分析评估了TNBC与非TNBC和正常乳腺细胞中硒蛋白mRNA的表达，在TNBC组织与正常组织中。免疫组织化学用于研究TNBC组织中的硒蛋白。STRING和Cytoscape工具用于功能和网络分析。
结果：GPX1，GPX4，SELENOS，TXNRD1和TXNRD3在TNBC细胞中特异性过表达，组织和CCLE/LINCS数据集。网络分析表明，SELENOS结合含有效球蛋白的蛋白（VCP/p97）在TNBC硒蛋白亚网络中起着关键的枢纽作用，与SELENOS表达直接相关。SELENOS和VCP/p97的联合过表达与TNBC组织和TCGA数据集中的晚期和不良预后相关。
结论：联合评估SELENOS和VCP/p97可能代表了一种新的潜在预后特征和TNBC的治疗靶点。
