Abstract
BackgroundLuminal B cancers show much worse outcomes compared to luminal A. This present study aims to screen key lncRNAs and mRNAs correlated with luminal-B breast cancer.MethodsLuminal-B breast cancer tissue samples and adjacent tissue samples were obtained from 4 patients with luminal-B breast cancer. To obtain differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) between luminal-B breast cancer tumor tissues and adjacent tissues, RNA-sequencing and bioinformatics analysis were performed. Functional annotation of DEmRNAs and protein-protein interaction networks (PPI) construction were performed. DEmRNAs transcribed within a 100 kb window up- or down-stream of DElncRNAs were searched, which were defined as cis nearby-targeted DEmRNAs of DElncRNAs. DElncRNA-DEmRNA co-expression networks were performed. The mRNA and lncRNA expression profiles were downloaded from The Cancer Genome Atlas (TCGA) database to validate the expression patterns of selected DEmRNAs and DElncRNAs.ResultsA total of 1178 DEmRNAs and 273 DElncRNAs between luminal-B breast cancer tumor tissues and adjacent tissues were obtained. Hematopoietic cell lineage, Cytokine-cytokine receptor interaction, Cell adhesion molecules (CAMs) and Primary immunodeficiency were significantly enriched KEGG pathways in luminal-B breast cancer. FN1, EGFR, JAK3, TUBB3 and PTPRC were five hub proteins of the PPI networks. A total of 99 DElncRNAs-nearby-targeted DEmRNA pairs and 1878 DElncRNA-DEmRNA co-expression pairs were obtained. Gene expression results validated in TCGA database were consistent with our RNA-sequencing results, generally.ConclusionThis study determined key genes and lncRNAs involved in luminal-B breast cancer, which expected to present a new avenue for the diagnosis and treatment of luminal-B breast cancer.
Highlights
Luminal B cancers show much worse outcomes compared to luminal A
The top 10 up- and down-regulated Differentially expressed mRNA (DEmRNA) and DElncRNAs were exhibited in Table 2 and Table 3, respectively
Hierarchical clustering analysis of top 100 10 up- and down-regulated DEmRNAs and DElncRNAs was showed in Fig. 1a and Fig. 1b, respectively
Summary
Luminal B cancers show much worse outcomes compared to luminal A. Breast cancer is the leading cause of cancer-related death in women, both overall and in less developed countries [1] It is a heterogeneous disease with regard to molecular alterations, cellular composition, and clinical outcome, both between tumor subtypes and within a single tumor, which were commonly defined by gene expression profiling as four main subtypes including luminal A, luminal B, HER-2 enriched and basal-like, Expression profiles and gene sets, with prognostic, predictive functions, or both for patients with breast cancer, have been identified in multiple studies [6] Both luminal-A and luminal-B breast cancers are ER-positive, luminal-B cancers showed worse outcomes as compared to luminal-A cancers [7, 8]. It is urgent to discover novel biomarkers with prognostic and predictive functions for luminal B breast cancer that can be therapeutically targeted
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