A Long Noncoding RNA Signature That Predicts Pathological Complete Remission Rate Sensitively in Neoadjuvant Treatment of Breast Cancer

BACKGROUND: Mounting evidence suggests that long noncoding RNAs (lncRNAs) are closely related to pathological complete response (pCR) in neoadjuvant treatment of breast cancer. Here, we construct lncRNA associated models to predict pCR rate. METHODS: LncRNA expression profiles of breast cancer patie...

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Main Authors: Gen Wang, Xiaosong Chen, Yue Liang, Wei Wang, Kunwei Shen
Format: Article
Language:English
Published: Elsevier 2017-12-01
Series:Translational Oncology
Online Access:http://www.sciencedirect.com/science/article/pii/S193652331730270X
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author Gen Wang
Xiaosong Chen
Yue Liang
Wei Wang
Kunwei Shen
author_facet Gen Wang
Xiaosong Chen
Yue Liang
Wei Wang
Kunwei Shen
author_sort Gen Wang
collection DOAJ
description BACKGROUND: Mounting evidence suggests that long noncoding RNAs (lncRNAs) are closely related to pathological complete response (pCR) in neoadjuvant treatment of breast cancer. Here, we construct lncRNA associated models to predict pCR rate. METHODS: LncRNA expression profiles of breast cancer patients treated with neoadjuvant chemotherapy (NAC) were obtained from Gene Expression Omnibus by repurposing existing microarray data. The prediction model was firstly built by analyzing the correlation between pCR and lncRNA expression in the discovery dataset GSE 25066 (n = 488). Another three independent datasets, GSE20194 (n = 278), GSE20271 (n = 178), and GSE22093 (n = 97), were integrated as the validation cohort to assess the prediction efficiency. RESULTS: A novel lncRNA signature (LRS) consisting of 36 lncRNAs was identified. Based on this LRS, patients with NAC treatment were divided into two groups: LRS-high group and LRS-low group, with positive correlation of pCR rate in the discovery dataset. In the validation cohort, univariate and multivariate analyses both demonstrated that high LRS was associated with higher pCR rate. Subgroup analysis confirmed that this model performed well in luminal B [odds ratio (OR) = 5.4; 95% confidence interval (CI) = 2.7-10.8; P = 1.47e-06], HER2-enriched (OR = 2.5; 95% CI = 1.1-5.7; P = .029), and basal-like (OR = 5.5; 95% CI = 2.3-16.2; P = 5.32e-04) subtypes. Compared with other preexisting prediction models, LRS demonstrated better performance with higher area under the curve. Functional annotation analysis suggested that lncRNAs in this signature were mainly involved in cancer proliferation process. CONCLUSION: Our findings indicated that our lncRNA signature was sensitive to predict pCR rate in the neoadjuvant treatment of breast cancer, which deserves further evaluation.
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spelling doaj.art-5011e3e14eaf41a2826933b57ec99d5d2022-12-22T02:58:50ZengElsevierTranslational Oncology1936-52331944-71242017-12-0110698899710.1016/j.tranon.2017.09.005A Long Noncoding RNA Signature That Predicts Pathological Complete Remission Rate Sensitively in Neoadjuvant Treatment of Breast CancerGen Wang0Xiaosong Chen1Yue Liang2Wei Wang3Kunwei Shen4Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR ChinaComprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR ChinaComprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR ChinaComprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR ChinaComprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR ChinaBACKGROUND: Mounting evidence suggests that long noncoding RNAs (lncRNAs) are closely related to pathological complete response (pCR) in neoadjuvant treatment of breast cancer. Here, we construct lncRNA associated models to predict pCR rate. METHODS: LncRNA expression profiles of breast cancer patients treated with neoadjuvant chemotherapy (NAC) were obtained from Gene Expression Omnibus by repurposing existing microarray data. The prediction model was firstly built by analyzing the correlation between pCR and lncRNA expression in the discovery dataset GSE 25066 (n = 488). Another three independent datasets, GSE20194 (n = 278), GSE20271 (n = 178), and GSE22093 (n = 97), were integrated as the validation cohort to assess the prediction efficiency. RESULTS: A novel lncRNA signature (LRS) consisting of 36 lncRNAs was identified. Based on this LRS, patients with NAC treatment were divided into two groups: LRS-high group and LRS-low group, with positive correlation of pCR rate in the discovery dataset. In the validation cohort, univariate and multivariate analyses both demonstrated that high LRS was associated with higher pCR rate. Subgroup analysis confirmed that this model performed well in luminal B [odds ratio (OR) = 5.4; 95% confidence interval (CI) = 2.7-10.8; P = 1.47e-06], HER2-enriched (OR = 2.5; 95% CI = 1.1-5.7; P = .029), and basal-like (OR = 5.5; 95% CI = 2.3-16.2; P = 5.32e-04) subtypes. Compared with other preexisting prediction models, LRS demonstrated better performance with higher area under the curve. Functional annotation analysis suggested that lncRNAs in this signature were mainly involved in cancer proliferation process. CONCLUSION: Our findings indicated that our lncRNA signature was sensitive to predict pCR rate in the neoadjuvant treatment of breast cancer, which deserves further evaluation.http://www.sciencedirect.com/science/article/pii/S193652331730270X
spellingShingle Gen Wang
Xiaosong Chen
Yue Liang
Wei Wang
Kunwei Shen
A Long Noncoding RNA Signature That Predicts Pathological Complete Remission Rate Sensitively in Neoadjuvant Treatment of Breast Cancer
Translational Oncology
title A Long Noncoding RNA Signature That Predicts Pathological Complete Remission Rate Sensitively in Neoadjuvant Treatment of Breast Cancer
title_full A Long Noncoding RNA Signature That Predicts Pathological Complete Remission Rate Sensitively in Neoadjuvant Treatment of Breast Cancer
title_fullStr A Long Noncoding RNA Signature That Predicts Pathological Complete Remission Rate Sensitively in Neoadjuvant Treatment of Breast Cancer
title_full_unstemmed A Long Noncoding RNA Signature That Predicts Pathological Complete Remission Rate Sensitively in Neoadjuvant Treatment of Breast Cancer
title_short A Long Noncoding RNA Signature That Predicts Pathological Complete Remission Rate Sensitively in Neoadjuvant Treatment of Breast Cancer
title_sort long noncoding rna signature that predicts pathological complete remission rate sensitively in neoadjuvant treatment of breast cancer
url http://www.sciencedirect.com/science/article/pii/S193652331730270X
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