An Integrated In Silico, In Vitro and Tumor Tissues Study Identified Selenoprotein S (SELENOS) and Valosin-Containing Protein (VCP/p97) as Novel Potential Associated Prognostic Biomarkers in Triple Negative Breast Cancer.
An Integrated In Silico, In Vitro and Tumor Tissues Study Identified Selenoprotein S (SELENOS) and Valosin-Containing Protein (VCP/p97) as Novel Potential Associated Prognostic Biomarkers in Triple Negative Breast Cancer.
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DOI：
10.3390/cancers14030646
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发表时间：
2022-01-27
期刊：
影响因子：
5.2
通讯作者：
Budillon A
中科院分区：
文献类型：
--
作者：
Costantini S;Polo A;Capone F;Accardo M;Sorice A;Lombardi R;Bagnara P;Zito Marino F;Amato M;Orditura M;Fratelli M;Ciliberto G;Budillon A
三阴性乳腺癌（TNBC）是一个临床挑战，因为它的早期复发，总生存率低，缺乏有效的治疗。硒蛋白水平的改变与某些癌症的发生和进展相关，然而，关于它们参与TNBC的情况没有一致的数据。在这里，我们分析了所有25个人硒蛋白在TNBC细胞和组织中的表达谱，通过系统的方法，整合在计算机和湿实验室的方法。我们发现，五个硒蛋白的表达谱在TNBC中特异性失调。最重要的是，通过生物信息学分析，我们选择了硒蛋白S及其相互作用蛋白Valosin-containing蛋白（VCP/p97）与其他蛋白相互关联，并且其协调过表达与TNBC的不良预后相关。总之，我们强调了两种机制相关的新蛋白，其相关表达可用于更好地定义预后，并建议作为TNBC的新治疗靶点。背景三阴性乳腺癌（TNBC）是一组异质性肿瘤，具有早期复发、总体生存率低和缺乏有效治疗的特点。因此，需要新的预后生物标志物和治疗靶点。方法.通过系统方法分析了所有25种人类硒蛋白在TNBC中的表达谱，对公开可用的mRNA表达数据集（Cancer Cell Line Encyclopedia，CCLE和Library of Integrated Network-based Cellular Signatures，LINCS）进行计算机分析。逆转录定量PCR分析评价了TNBC与非TNBC和正常乳腺细胞中以及TNBC组织与正常对应物中的硒蛋白mRNA表达。采用免疫组织化学方法研究TNBC组织中的硒蛋白。使用STRING和Cytoscape工具进行功能和网络分析。结果：GPX 1、GPX 4、SELENOS、TXNRD 1和TXNRD 3在TNBC细胞、组织和CCLE/LINCS数据集中特异性过表达。网络分析表明，含SELENOS结合valosin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。在TNBC组织和TCGA数据集中，SELENOS和VCP/p97的联合过表达与晚期和预后不良相关。结论SELENOS和VCP/p97的联合评价可能代表了一种新的潜在预后标志和TNBC的治疗靶点。
Triple negative breast cancer (TNBC) represents a clinical challenge because its early relapse, poor overall survival and lack of effective treatments. Altered levels selenoproteins have been correlated with development and progression of some cancers, however, no consistent data are available about their involvement in TNBC. Here we analyzed the expression profile of all twenty-five human selenoproteins in TNBC cells and tissues by a systematic approach, integrating in silico and wet lab approaches. We showed that the expression profiles of five selenoproteins are specifically dysregulated in TNBC. Most importantly, by a bioinformatics analysis, we selected selenoprotein S and its interacting protein valosin-containing protein (VCP/p97) as inter-related with the others and whose coordinated over-expression is associated with poor prognosis in TNBC. Overall, we highlighted two mechanistically related novel proteins whose correlated expression could be exploited for a better definition of prognosis as well as suggested as novel therapeutic target in TNBC. 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. Conclusion. Combined evaluation of SELENOS and VCP/p97 might represent a novel potential prognostic signature and a therapeutic target to be exploited in TNBC.
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DOI：
10.1016/j.bbrc.2007.03.018
发表时间：
2007-05-11
影响因子：
3.1
作者：
Gao, Yuan;Pagnon, Joanne;Collier, Greg R.
通讯作者：
Collier, Greg R.
影响因子：
8
作者：
Howley BV;Link LA;Grelet S;El-Sabban M;Howe PH
通讯作者：
Howe PH
影响因子：
5.6
作者：
Costantini S;Capone F;Polo A;Bagnara P;Budillon A
通讯作者：
Budillon A
DOI：
10.3390/molecules20023027
发表时间：
2015-02-12
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Chapman E;Maksim N;de la Cruz F;La Clair JJ
通讯作者：
La Clair JJ
影响因子：
--
作者：
Cui, Yan;Niu, Ming;Pang, Da
通讯作者：
Pang, Da