Abstract

BackgroundLong noncoding RNAs (lncRNAs) are emerging as crucial contributors to the development of breast cancer and are involved in the stemness regulation of breast cancer stem cells (BCSCs). LncRNAs are closely associated with the prognosis of breast cancer patients. It is critical to identify BCSC-related lncRNAs with prognostic value in breast cancer.MethodsA co-expression network of BCSC-related mRNAs-lncRNAs from The Cancer Genome Atlas (TCGA) was constructed. Univariate and multivariate Cox proportional hazards analyses were used to identify a stemness risk model with prognostic value. Kaplan–Meier analysis, univariate and multivariate Cox regression analyses and receiver operating characteristic (ROC) curve analysis were performed to validate the risk model. Principal component analysis (PCA) and Gene Set Enrichment Analysis (GSEA) functional annotation were conducted to analyze the risk model.ResultsIn this study, BCSC-related lncRNAs in breast cancer were identified. We evaluated the prognostic value of these BCSC-related lncRNAs and eventually obtained a prognostic risk model consisting of 12 BCSC-related lncRNAs (Z68871.1, LINC00578, AC097639.1, AP003119.3, AP001207.3, LINC00668, AL122010.1, AC245297.3, LINC01871, AP000851.2, AC022509.2 and SEMA3B-AS1). The risk model was further verified as a novel independent prognostic factor for breast cancer patients based on the calculated risk score. Moreover, based on the risk model, the low- risk and high-risk groups displayed different stemness statuses.ConclusionsThese findings suggested that the 12 BCSC-related lncRNA signature might be a promising prognostic factor for breast cancer and can promote the management of BCSC-related therapy in clinical practice.

Highlights

  • Long noncoding RNAs are emerging as crucial contributors to the development of breast cancer and are involved in the stemness regulation of breast cancer stem cells (BCSCs)

  • Identification of significant prognostic value of BCSC‐related Long noncoding RNAs (lncRNAs) in breast cancer A total of 1198 BCSC-related lncRNAs were obtained by constructing co-expression networks with 213 BCSCrelated encoding genes (Additional files 1, 2 and 3)

  • 32 BCSC-related lncRNAs were significantly associated with the survival of breast cancer patients from the The Cancer Genome Atlas (TCGA) (p < 0.01) by Cox proportional hazards analysis, including 23 lncRNAs with low risk (hazard ratio (HR) < 1) and 9 lncRNAs with high risk (HR > 1) (Fig. 1)

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Summary

Introduction

Long noncoding RNAs (lncRNAs) are emerging as crucial contributors to the development of breast cancer and are involved in the stemness regulation of breast cancer stem cells (BCSCs). LncRNAs are closely associated with the prognosis of breast cancer patients. It is critical to identify BCSC-related lncRNAs with prognostic value in breast cancer. The identification of novel prognostic biomarkers and Heterogeneity is a hallmark of solid tumors, including breast cancer, which results from the enrichment of cancer stem cells (CSCs) [3, 4]. Breast cancer stem cells (BCSCs) are considered the source of tumor aggression, metastasis, worse prognosis, chemoresistance and recurrence in breast cancer [6]. Identifying key stemness regulators of BCSCs is of great importance for both theoretical studies and clinical practice

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