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.
Highlights
Breast cancer (BC) is one of the most common malignant tumors and the main cause of cancer-associated death in women worldwide
By taking advantage of the RNA sequencing (RNA-Seq) and clinical data of 566 luminal BC tumor samples from The Cancer Genome Atlas (TCGA) database and the ESTIMATE algorithm, we aimed to explore the association between overall survival and immune scores (ISs) and stromal scores (SSs) of luminal BC and construct a competing endogenous RNAs (ceRNAs) network of differentially expressed messenger RNAs (mRNAs) (DEmRNAs), long noncoding RNAs (lncRNAs) (DElncRNAs), and miRNAs (DEmiRNAs) related to the ISs and SSs
The RNA sequencing datasets downloaded from TCGA database consisted of 556 luminal BC samples, of which 381 were luminal A and 175 were luminal B samples
Summary
Breast cancer (BC) is one of the most common malignant tumors and the main cause of cancer-associated death in women worldwide. Treatment measures for BC patients, such as surgical methods and drug regimens, have been constantly improved, while the clinical outcomes of individual patients remain difficult to predict (Clough et al, 2010; Graham et al, 2015). BC is a heterogeneous disease in terms of cellular composition, molecular alterations, and clinical outcomes within different tumor subtypes and within a single tumor. The recurrent risk of luminal BC patients can be reduced by endocrine therapy, some patients still relapse after 5 years. 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)
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