Wang Yanyan, Zhu Mingzhi, Guo Feng, Song Yi, Fan Xunjie, Qin Guijun
Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Front Genet. 2020 Nov 10;11:555865. doi: 10.3389/fgene.2020.555865. eCollection 2020.
The tumor microenvironment (TME) has been reported to have significant value in the diagnosis and prognosis of cancers. This study aimed to identify key biomarkers in the TME of luminal breast cancer (BC). We obtained immune scores (ISs) and stromal scores (SSs) for The Cancer Genome Atlas (TCGA) luminal BC cohort from the online ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) portal. The relationships between ISs and SSs and the overall survival of luminal BC patients were assessed by the Kaplan-Meier method. The differentially expressed messenger RNAs (DEmRNAs) related to the ISs and SSs were subjected to functional enrichment analysis. Additionally, a competing endogenous RNA (ceRNA) network was constructed with differentially expressed microRNAs (DEmiRNAs) and long noncoding RNAs (DElncRNAs). Furthermore, a protein-protein interaction (PPI) network was established to analyze the DEmRNAs in the ceRNA network. Then, survival analysis of biomarkers involved in the ceRNA network was carried out to explore their prognostic value. Finally, these biomarkers were validated using the luminal BC dataset from the Gene Expression Omnibus (GEO) database. The results showed that ISs were significantly associated with longer survival times of luminal BC patients. Functional enrichment analysis showed that the DEmRNAs were mainly associated with immune response, antigen binding, and the extracellular region. In the PPI network, the top 10 DEmRNAs were identified as hub genes that affected the TME of luminal BC. Finally, two DEmiRNAs, two DElncRNAs, and 17 DEmRNAs of the ceRNA network associated with the TME were shown to have prognostic value. Subsequently, the expression of 15 prognostic biomarkers was validated in one additional dataset (GSE81002). In particular, one lncRNA (GVINP1) and five mRNAs (CCDC69, DOCK2, IKZF1, JCHAIN, and NCKAP1L) were novel biomarkers. Our studies demonstrated that ISs were associated with the survival of luminal BC patients, and a set of novel biomarkers that might play a prognostic role in the TME of luminal BC was identified.
据报道，肿瘤微环境（TME）在癌症的诊断和预后方面具有重要价值。本研究旨在确定管腔型乳腺癌（BC）的TME中的关键生物标志物。我们从在线ESTIMATE（使用表达数据估计恶性肿瘤组织中的基质和免疫细胞）门户获取了癌症基因组图谱（TCGA）管腔型BC队列的免疫评分（ISs）和基质评分（SSs）。采用Kaplan-Meier方法评估ISs和SSs与管腔型BC患者总生存期之间的关系。对与ISs和SSs相关的差异表达信使RNA（DEmRNAs）进行功能富集分析。此外，构建了一个由差异表达微小RNA（DEmiRNAs）和长链非编码RNA（DElncRNAs）组成的竞争性内源RNA（ceRNA）网络。此外，建立了蛋白质-蛋白质相互作用（PPI）网络来分析ceRNA网络中的DEmRNAs。然后，对ceRNA网络中涉及的生物标志物进行生存分析，以探索它们的预后价值。最后，使用来自基因表达综合数据库（GEO）的管腔型BC数据集对这些生物标志物进行验证。结果表明，ISs与管腔型BC患者较长的生存时间显著相关。功能富集分析表明，DEmRNAs主要与免疫反应、抗原结合和细胞外区域相关。在PPI网络中，前10个DEmRNAs被确定为影响管腔型BC的TME的枢纽基因。最后，与TME相关的ceRNA网络中的两个DEmiRNAs、两个DElncRNAs和17个DEmRNAs显示具有预后价值。随后，在另一个数据集（GSE81002）中验证了15个预后生物标志物的表达。特别是，一个长链非编码RNA（GVINP1）和五个信使RNA（CCDC69、DOCK2、IKZF1、JCHAIN和NCKAP1L）是新的生物标志物。我们的研究表明，ISs与管腔型BC患者的生存相关，并鉴定出一组可能在管腔型BC的TME中发挥预后作用的新生物标志物。
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