lncRNA OSTN-AS1 May Represent a Novel Immune-Related Prognostic Marker for Triple-Negative Breast Cancer Based on Integrated Analysis of a ceRNA Network
lncRNA OSTN-AS1 May Represent a Novel Immune-Related Prognostic Marker for Triple-Negative Breast Cancer Based on Integrated Analysis of a ceRNA Network
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基于 ceRNA 网络的综合分析，lncRNA OSTN-AS1 可能代表三阴性乳腺癌的一种新型免疫相关预后标志物
DOI：
10.3389/fgene.2019.00850
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发表时间：
2019-09-13
影响因子：
3.7
通讯作者：
Zhang, Liling
中科院分区：
文献类型：
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作者：
Liu, Zijian;Mi, Mi;Zhang, Liling
竞争性内源性 RNA (ceRNA) 网络是研究癌症的有效方法；然而，之前尚未在不同乳腺癌亚型之间构建 ceRNA 网络。通过对从TCGA数据库下载的150个三阴性乳腺癌（TNBC）组织和823个非三阴性乳腺癌（nTNBC）组织之间差异表达RNA进行分析，使用Cytoscape基于数据库比较构建了ceRNA网络。结合生存分析和受试者工作特征曲线数据筛选出预后候选基因，随后使用共表达功能相关分析、基因集变异分析（GSVA）通路相关分析以及免疫浸润和肿瘤突变负荷免疫相关分析进行分析。 TNBC和nTNBC亚型之间的ceRNA网络中总共包含190个差异表达的lncRNA（DElncRNA）、48个差异表达的mRNA（DEmRNA）和13个差异表达的miRNA（DEmiRNA）。利用与预后候选lncRNA（AC104472.1、PSORS1C3、DSCR9、OSTN-AS1、AC012074.1、AC005035.1、SIAH2-AS1和ERVMER61-1）共表达的mRNA的基因本体分析进行功能预测。因此，OSTN-AS1主要与免疫功能相关，例如免疫细胞浸润和免疫相关标志物共表达。 GSVA偏差程度随着OSTN表达的增加而增加。此外，许多重要的免疫分子，例如PDCD1和CTLA-4，在其定量表达方面具有很强的相关性。竞争性内源性 RNA 网络可能会识别乳腺癌的候选治疗靶点和潜在的预后生物标志物。特别是OSTN-AS1作为一种新型免疫相关分子，未来可能参与免疫治疗工作。
The competing endogenous RNA (ceRNA) networks are an effective method for investigating cancer; however, construction of ceRNA networks among different subtypes of breast cancer has not been previously performed. Based on analysis of differentially expressed RNAs between 150 triple-negative breast cancer (TNBC) tissues and 823 non–triple-negative breast cancer (nTNBC) tissues downloaded from TCGA database, a ceRNA network was constructed based on database comparisons using Cytoscape. Survival analysis and receiver operating characteristic curve data were combined to screen out prognostic candidate genes, which were subsequently analyzed using co-expressed functionally related analysis, Gene Set Variation Analysis (GSVA) pathway-related analysis, and immune infiltration and tumor mutational burden immune-related analysis. A total of 190 differentially expressed lncRNAs (DElncRNAs), 48 differentially expressed mRNAs (DEmRNAs), and 13 differentially expressed miRNAs (DEmiRNAs) were included in the ceRNA network between TNBC and nTNBC subtypes. Gene ontology analysis of mRNAs coexpressed with prognostic candidate lncRNAs (AC104472.1, PSORS1C3, DSCR9, OSTN-AS1, AC012074.1, AC005035.1, SIAH2-AS1, and ERVMER61-1) were utilized for functional prediction. Consequently, OSTN-AS1 was primarily related to immunologic function, for instance, immune cell infiltration and immune-related markers coexpression. The GSVA deviation degree was increased with OSTN increased expression. In addition, many important immune molecules, such as PDCD1 and CTLA-4, were strongly correlated in terms of their quantitative expression. Competing endogenous RNA networks may identify candidate therapeutic targets and potential prognostic biomarkers in breast cancer. In particular, OSTN-AS1 serves as a novel immune-related molecule and could be involved in immunotherapy efforts in the future.