Exploration of epithelial-mesenchymal transition-related lncRNA signature and drug sensitivity in breast cancer

BackgroundBreast cancer (BRCA) has become the most diagnosed cancer worldwide for female and seriously endanger female health. The epithelial-mesenchymal transition (EMT) process is associated with metastasis and drug resistance in BRCA patients. However, the prognostic value of EMT-related lncRNA i...

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Main Authors: Chengxin Li, Lewei Zheng, Gaoran Xu, Qianqian Yuan, Ziyang Di, Yalong Yang, Xingxing Dong, Jinxuan Hou, Gaosong Wu
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-07-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2023.1154741/full
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author Chengxin Li
Lewei Zheng
Gaoran Xu
Qianqian Yuan
Ziyang Di
Yalong Yang
Xingxing Dong
Jinxuan Hou
Gaosong Wu
author_facet Chengxin Li
Lewei Zheng
Gaoran Xu
Qianqian Yuan
Ziyang Di
Yalong Yang
Xingxing Dong
Jinxuan Hou
Gaosong Wu
author_sort Chengxin Li
collection DOAJ
description BackgroundBreast cancer (BRCA) has become the most diagnosed cancer worldwide for female and seriously endanger female health. The epithelial-mesenchymal transition (EMT) process is associated with metastasis and drug resistance in BRCA patients. However, the prognostic value of EMT-related lncRNA in BRCA still needs to be revealed. The aim of this study is to construct an EMT-related lncRNA (ERL) signature with accuracy predictive ability for the prognosis of BRCA patients.MethodsRNA-seq expression data and Clinical characteristics obtained from the TCGA (The Cancer Genome Atlas) were used in the study. First, we identified the EMT-related lncRNA by the Pearson correlation analysis. An EMT-related lncRNAs prognostic risk signature was constructed using univariate Cox regression and Lasso-penalized Cox regression analyses. The model’s performance was validated using Kaplan-Meier (KM) survival analysis, ROC curve and C-index. Finally, a nomogram was constructed for clinical practice in evaluating the patients with BRCA and validated by calibration curve and decision curve analysis (DCA). We also evaluated the drug sensitivity of signature lncRNA and the tumor immune cell infiltration in breast cancer.ResultsWe constructed a 10-lncRNA risk score signature based on the lncRNAs associated with the EMT process. We could assign BRCA patients to the high- and low-risk group according to the median risk score. The prognostic risk signature showed excellent accuracy and demonstrated sufficient independence from other clinical characteristics. The immune cell infiltration analysis showed that the prognostic risk signature was related to the infiltration of the immune cell subtype. Drug sensitivity analysis proved ERLs signature could effectively predict the sensitivity of patients to common chemotherapy drugs in BRCA and provide guidance for chemotherapy drugs for high-risk and low-risk patients.ConclusionOur ERL signature and nomogram have excellent prognostic value and could become reliable tools for clinical guidance.
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spelling doaj.art-447e3aa3bc0a4527982f351eeb4caaa62023-07-19T08:25:57ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-07-011410.3389/fendo.2023.11547411154741Exploration of epithelial-mesenchymal transition-related lncRNA signature and drug sensitivity in breast cancerChengxin Li0Lewei Zheng1Gaoran Xu2Qianqian Yuan3Ziyang Di4Yalong Yang5Xingxing Dong6Jinxuan Hou7Gaosong Wu8Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Gastrointestinal Surgery and Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaBackgroundBreast cancer (BRCA) has become the most diagnosed cancer worldwide for female and seriously endanger female health. The epithelial-mesenchymal transition (EMT) process is associated with metastasis and drug resistance in BRCA patients. However, the prognostic value of EMT-related lncRNA in BRCA still needs to be revealed. The aim of this study is to construct an EMT-related lncRNA (ERL) signature with accuracy predictive ability for the prognosis of BRCA patients.MethodsRNA-seq expression data and Clinical characteristics obtained from the TCGA (The Cancer Genome Atlas) were used in the study. First, we identified the EMT-related lncRNA by the Pearson correlation analysis. An EMT-related lncRNAs prognostic risk signature was constructed using univariate Cox regression and Lasso-penalized Cox regression analyses. The model’s performance was validated using Kaplan-Meier (KM) survival analysis, ROC curve and C-index. Finally, a nomogram was constructed for clinical practice in evaluating the patients with BRCA and validated by calibration curve and decision curve analysis (DCA). We also evaluated the drug sensitivity of signature lncRNA and the tumor immune cell infiltration in breast cancer.ResultsWe constructed a 10-lncRNA risk score signature based on the lncRNAs associated with the EMT process. We could assign BRCA patients to the high- and low-risk group according to the median risk score. The prognostic risk signature showed excellent accuracy and demonstrated sufficient independence from other clinical characteristics. The immune cell infiltration analysis showed that the prognostic risk signature was related to the infiltration of the immune cell subtype. Drug sensitivity analysis proved ERLs signature could effectively predict the sensitivity of patients to common chemotherapy drugs in BRCA and provide guidance for chemotherapy drugs for high-risk and low-risk patients.ConclusionOur ERL signature and nomogram have excellent prognostic value and could become reliable tools for clinical guidance.https://www.frontiersin.org/articles/10.3389/fendo.2023.1154741/fullepithelial-mesenchymal transitionbreast cancerlong non-coding RNAprognostic modeldrug sensitivity
spellingShingle Chengxin Li
Lewei Zheng
Gaoran Xu
Qianqian Yuan
Ziyang Di
Yalong Yang
Xingxing Dong
Jinxuan Hou
Gaosong Wu
Exploration of epithelial-mesenchymal transition-related lncRNA signature and drug sensitivity in breast cancer
Frontiers in Endocrinology
epithelial-mesenchymal transition
breast cancer
long non-coding RNA
prognostic model
drug sensitivity
title Exploration of epithelial-mesenchymal transition-related lncRNA signature and drug sensitivity in breast cancer
title_full Exploration of epithelial-mesenchymal transition-related lncRNA signature and drug sensitivity in breast cancer
title_fullStr Exploration of epithelial-mesenchymal transition-related lncRNA signature and drug sensitivity in breast cancer
title_full_unstemmed Exploration of epithelial-mesenchymal transition-related lncRNA signature and drug sensitivity in breast cancer
title_short Exploration of epithelial-mesenchymal transition-related lncRNA signature and drug sensitivity in breast cancer
title_sort exploration of epithelial mesenchymal transition related lncrna signature and drug sensitivity in breast cancer
topic epithelial-mesenchymal transition
breast cancer
long non-coding RNA
prognostic model
drug sensitivity
url https://www.frontiersin.org/articles/10.3389/fendo.2023.1154741/full
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