Abstract

Long non-coding RNAs (lncRNAs) have been well known for their multiple functions in the tumorigenesis, development, and prognosis of breast cancer (BC). Mechanistically, their production, function, or stability can be regulated by RNA binding proteins (RBPs), which were also involved in the carcinogenesis and progression of BC. However, the roles and clinical implications of RBP-related lncRNAs in BC remain largely unknown. Therefore, we herein aim to construct a prognostic signature with RBP-relevant lncRNAs for the prognostic evaluation of BC patients. Firstly, based on the RNA sequencing data of female BC patients from The Cancer Genome Atlas (TCGA) database, we screened out 377 differentially expressed lncRNAs related to RBPs. The univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses were then performed to establish a prognostic signature composed of 12-RBP-related lncRNAs. Furthermore, we divided the BC patients into high- and low-risk groups by the prognostic signature and found the overall survival (OS) of patients in the high-risk group was significantly shorter than that of the low-risk group. Moreover, the 12-lncRNA signature exhibited independence in evaluating the prognosis of BC patients. Additionally, a functional enrichment analysis revealed that the prognostic signature was associated with some cancer-relevant pathways, including cell cycle and immunity. In summary, our 12-lncRNA signature may provide a theoretical reference for the prognostic evaluation or clinical treatment of BC patients.

Highlights

  • Female breast cancer (BC) has become the leading cause of global cancer incidence in2020, with approximately 2.3 million new cases and 685,000 deaths [1]

  • As for the PAM50 subtype, we found that patients in the high-risk groups had a poorer prognosis in these subtypes, including luminal A, normal-like, and basal-like (Figure S4A–C)

  • We investigated which biological processes were associated with the risk score to reveal the possible mechanisms that affected the prognosis of BC patients

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Summary

Introduction

Female breast cancer (BC) has become the leading cause of global cancer incidence in2020, with approximately 2.3 million new cases and 685,000 deaths [1]. Female breast cancer (BC) has become the leading cause of global cancer incidence in. Metastasis and local or distant recurrence of tumors are the leading causes of mortality for BC patients [2]. BC is a highly heterogeneous tumor on the molecular level. Through the PAM50 classification system based on a 50-gene expression signature, current clinical practice has usually classified BC into five subtypes, including luminal A, luminal B, HER2-enriched, normallike, and basal-like (triple-negative BC) [3]. As there is a heterogeneity of treatment response within the same subtype [2], the BC subtype still needs more exploration to obtain a higher therapeutic effect. There is an urgent requirement to discover more prognostic signatures, which can stratify female BC patients to improve the prognosis of high-risk patients and minimize the overtreatment of low-risk patients

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