Identification of a Six-lncRNA Signature With Prognostic Value for Breast Cancer Patients

Breast cancer (BRCA) is the most common cancer and a major cause of death in women. Long non-coding RNAs (lncRNAs) are emerging as key regulators and have been implicated in carcinogenesis and prognosis. In this study, we aimed to develop a lncRNA signature of BRCA patients to improve risk stratific...

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Main Authors: Erjie Zhao, Yujia Lan, Fei Quan, Xiaojing Zhu, Suru A, Linyun Wan, Jinyuan Xu, Jing Hu
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-07-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fgene.2020.00673/full
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spelling doaj-84f3cc0f56684f9bb228693c38ac362a2020-11-25T03:29:25ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-07-011110.3389/fgene.2020.00673540319Identification of a Six-lncRNA Signature With Prognostic Value for Breast Cancer PatientsErjie ZhaoYujia LanFei QuanXiaojing ZhuSuru ALinyun WanJinyuan XuJing HuBreast cancer (BRCA) is the most common cancer and a major cause of death in women. Long non-coding RNAs (lncRNAs) are emerging as key regulators and have been implicated in carcinogenesis and prognosis. In this study, we aimed to develop a lncRNA signature of BRCA patients to improve risk stratification. In the training cohort (GSE21653, n = 232), 17 lncRNAs were identified by univariate Cox proportional hazards regression, which were significantly associated with patients’ survival. The least absolute shrinkage and selection operator-penalized Cox proportional hazards regression analysis was used to identify a six-lncRNA signature. According to the median of the signature risk score, patients were divided into a high-risk group and a low-risk group with significant disease-free survival differences in the training cohort. A similar phenomenon was observed in validation cohorts (GSE42568, n = 101; GSE20711, n = 87). The six-lncRNA signature remained as independent prognostic factors after adjusting for clinical factors in these two cohorts. Furthermore, this signature significantly predicted the survival of grade III patients and estrogen receptor-positive patients. Furthermore, in another cohort (GSE19615, n = 115), the low-risk patients that were treated with tamoxifen therapy had longer disease-free survival than those who underwent no therapy. Overall, the six-lncRNA signature can be a potential prognostic tool used to predict disease-free survival of patients and to predict the benefits of tamoxifen treatment in BRCA, which will be helpful in guiding individualized treatments for BRCA patients.https://www.frontiersin.org/article/10.3389/fgene.2020.00673/fulllong non-coding RNAsignatureprognosisdisease-free survivalbreast cancer
collection DOAJ
language English
format Article
sources DOAJ
author Erjie Zhao
Yujia Lan
Fei Quan
Xiaojing Zhu
Suru A
Linyun Wan
Jinyuan Xu
Jing Hu
spellingShingle Erjie Zhao
Yujia Lan
Fei Quan
Xiaojing Zhu
Suru A
Linyun Wan
Jinyuan Xu
Jing Hu
Identification of a Six-lncRNA Signature With Prognostic Value for Breast Cancer Patients
Frontiers in Genetics
long non-coding RNA
signature
prognosis
disease-free survival
breast cancer
author_facet Erjie Zhao
Yujia Lan
Fei Quan
Xiaojing Zhu
Suru A
Linyun Wan
Jinyuan Xu
Jing Hu
author_sort Erjie Zhao
title Identification of a Six-lncRNA Signature With Prognostic Value for Breast Cancer Patients
title_short Identification of a Six-lncRNA Signature With Prognostic Value for Breast Cancer Patients
title_full Identification of a Six-lncRNA Signature With Prognostic Value for Breast Cancer Patients
title_fullStr Identification of a Six-lncRNA Signature With Prognostic Value for Breast Cancer Patients
title_full_unstemmed Identification of a Six-lncRNA Signature With Prognostic Value for Breast Cancer Patients
title_sort identification of a six-lncrna signature with prognostic value for breast cancer patients
publisher Frontiers Media S.A.
series Frontiers in Genetics
issn 1664-8021
publishDate 2020-07-01
description Breast cancer (BRCA) is the most common cancer and a major cause of death in women. Long non-coding RNAs (lncRNAs) are emerging as key regulators and have been implicated in carcinogenesis and prognosis. In this study, we aimed to develop a lncRNA signature of BRCA patients to improve risk stratification. In the training cohort (GSE21653, n = 232), 17 lncRNAs were identified by univariate Cox proportional hazards regression, which were significantly associated with patients’ survival. The least absolute shrinkage and selection operator-penalized Cox proportional hazards regression analysis was used to identify a six-lncRNA signature. According to the median of the signature risk score, patients were divided into a high-risk group and a low-risk group with significant disease-free survival differences in the training cohort. A similar phenomenon was observed in validation cohorts (GSE42568, n = 101; GSE20711, n = 87). The six-lncRNA signature remained as independent prognostic factors after adjusting for clinical factors in these two cohorts. Furthermore, this signature significantly predicted the survival of grade III patients and estrogen receptor-positive patients. Furthermore, in another cohort (GSE19615, n = 115), the low-risk patients that were treated with tamoxifen therapy had longer disease-free survival than those who underwent no therapy. Overall, the six-lncRNA signature can be a potential prognostic tool used to predict disease-free survival of patients and to predict the benefits of tamoxifen treatment in BRCA, which will be helpful in guiding individualized treatments for BRCA patients.
topic long non-coding RNA
signature
prognosis
disease-free survival
breast cancer
url https://www.frontiersin.org/article/10.3389/fgene.2020.00673/full
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