Identification of Tumor Microenvironment-Related Prognostic Biomarkers in Luminal Breast Cancer

Yanyan Wang; Mingzhi Zhu; Feng Guo; Yi Song; Xunjie Fan; Guijun Qin

doi:10.3389/fgene.2020.555865

Identification of Tumor Microenvironment-Related Prognostic Biomarkers in Luminal Breast Cancer

Front Genet. 2020 Nov 10:11:555865. doi: 10.3389/fgene.2020.555865. eCollection 2020.

Authors

Yanyan Wang¹, Mingzhi Zhu¹, Feng Guo², Yi Song², Xunjie Fan², Guijun Qin²

Affiliations

¹ Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
² Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Abstract

Background: 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). Methods: 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. Results: 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. Conclusions: 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.

Keywords: ESTIMATE algorithm; long noncoding RNA; luminal breast cancer; messenger RNA; microRNA; tumor microenvironment.