Radiogenomics analysis reveals the associations of dynamic contrast-enhanced–MRI features with gene expression characteristics, PAM50 subtypes, and prognosis of breast cancer

BackgroundTo investigate reliable associations between dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) features and gene expression characteristics in breast cancer (BC) and to develop and validate classifiers for predicting PAM50 subtypes and prognosis from DCE-MRI non-invasively.Met...

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Main Authors: Wenlong Ming, Yanhui Zhu, Yunfei Bai, Wanjun Gu, Fuyu Li, Zixi Hu, Tiansong Xia, Zuolei Dai, Xiafei Yu, Huamei Li, Yu Gu, Shaoxun Yuan, Rongxin Zhang, Haitao Li, Wenyong Zhu, Jianing Ding, Xiao Sun, Yun Liu, Hongde Liu, Xiaoan Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-07-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2022.943326/full
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author Wenlong Ming
Yanhui Zhu
Yunfei Bai
Wanjun Gu
Wanjun Gu
Fuyu Li
Zixi Hu
Tiansong Xia
Zuolei Dai
Xiafei Yu
Huamei Li
Yu Gu
Shaoxun Yuan
Rongxin Zhang
Haitao Li
Wenyong Zhu
Jianing Ding
Xiao Sun
Yun Liu
Hongde Liu
Xiaoan Liu
author_facet Wenlong Ming
Yanhui Zhu
Yunfei Bai
Wanjun Gu
Wanjun Gu
Fuyu Li
Zixi Hu
Tiansong Xia
Zuolei Dai
Xiafei Yu
Huamei Li
Yu Gu
Shaoxun Yuan
Rongxin Zhang
Haitao Li
Wenyong Zhu
Jianing Ding
Xiao Sun
Yun Liu
Hongde Liu
Xiaoan Liu
author_sort Wenlong Ming
collection DOAJ
description BackgroundTo investigate reliable associations between dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) features and gene expression characteristics in breast cancer (BC) and to develop and validate classifiers for predicting PAM50 subtypes and prognosis from DCE-MRI non-invasively.MethodsTwo radiogenomics cohorts with paired DCE-MRI and RNA-sequencing (RNA-seq) data were collected from local and public databases and divided into discovery (n = 174) and validation cohorts (n = 72). Six external datasets (n = 1,443) were used for prognostic validation. Spatial–temporal features of DCE-MRI were extracted, normalized properly, and associated with gene expression to identify the imaging features that can indicate subtypes and prognosis.ResultsExpression of genes including RBP4, MYBL2, and LINC00993 correlated significantly with DCE-MRI features (q-value < 0.05). Importantly, genes in the cell cycle pathway exhibited a significant association with imaging features (p-value < 0.001). With eight imaging-associated genes (CHEK1, TTK, CDC45, BUB1B, PLK1, E2F1, CDC20, and CDC25A), we developed a radiogenomics prognostic signature that can distinguish BC outcomes in multiple datasets well. High expression of the signature indicated a poor prognosis (p-values < 0.01). Based on DCE-MRI features, we established classifiers to predict BC clinical receptors, PAM50 subtypes, and prognostic gene sets. The imaging-based machine learning classifiers performed well in the independent dataset (areas under the receiver operating characteristic curve (AUCs) of 0.8361, 0.809, 0.7742, and 0.7277 for estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2)-enriched, basal-like, and obtained radiogenomics signature). Furthermore, we developed a prognostic model directly using DCE-MRI features (p-value < 0.0001).ConclusionsOur results identified the DCE-MRI features that are robust and associated with the gene expression in BC and displayed the possibility of using the features to predict clinical receptors and PAM50 subtypes and to indicate BC prognosis.
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spelling doaj.art-e68cc9c9fd5c4d02966355f557cd18bb2022-12-22T02:50:01ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-07-011210.3389/fonc.2022.943326943326Radiogenomics analysis reveals the associations of dynamic contrast-enhanced–MRI features with gene expression characteristics, PAM50 subtypes, and prognosis of breast cancerWenlong Ming0Yanhui Zhu1Yunfei Bai2Wanjun Gu3Wanjun Gu4Fuyu Li5Zixi Hu6Tiansong Xia7Zuolei Dai8Xiafei Yu9Huamei Li10Yu Gu11Shaoxun Yuan12Rongxin Zhang13Haitao Li14Wenyong Zhu15Jianing Ding16Xiao Sun17Yun Liu18Hongde Liu19Xiaoan Liu20State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, ChinaDepartment of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaState Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, ChinaState Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, ChinaCollaborative Innovation Center of Jiangsu Province of Cancer Prevention and Treatment of Chinese Medicine, School of Artificial Intelligence and Information Technology, Nanjing University of Chinese Medicine, Nanjing, ChinaState Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, ChinaState Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, ChinaDepartment of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Information, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaState Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, ChinaState Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, ChinaState Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, ChinaState Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, ChinaState Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, ChinaState Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, ChinaState Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, ChinaState Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, ChinaDepartment of Information, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaState Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, ChinaDepartment of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaBackgroundTo investigate reliable associations between dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) features and gene expression characteristics in breast cancer (BC) and to develop and validate classifiers for predicting PAM50 subtypes and prognosis from DCE-MRI non-invasively.MethodsTwo radiogenomics cohorts with paired DCE-MRI and RNA-sequencing (RNA-seq) data were collected from local and public databases and divided into discovery (n = 174) and validation cohorts (n = 72). Six external datasets (n = 1,443) were used for prognostic validation. Spatial–temporal features of DCE-MRI were extracted, normalized properly, and associated with gene expression to identify the imaging features that can indicate subtypes and prognosis.ResultsExpression of genes including RBP4, MYBL2, and LINC00993 correlated significantly with DCE-MRI features (q-value < 0.05). Importantly, genes in the cell cycle pathway exhibited a significant association with imaging features (p-value < 0.001). With eight imaging-associated genes (CHEK1, TTK, CDC45, BUB1B, PLK1, E2F1, CDC20, and CDC25A), we developed a radiogenomics prognostic signature that can distinguish BC outcomes in multiple datasets well. High expression of the signature indicated a poor prognosis (p-values < 0.01). Based on DCE-MRI features, we established classifiers to predict BC clinical receptors, PAM50 subtypes, and prognostic gene sets. The imaging-based machine learning classifiers performed well in the independent dataset (areas under the receiver operating characteristic curve (AUCs) of 0.8361, 0.809, 0.7742, and 0.7277 for estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2)-enriched, basal-like, and obtained radiogenomics signature). Furthermore, we developed a prognostic model directly using DCE-MRI features (p-value < 0.0001).ConclusionsOur results identified the DCE-MRI features that are robust and associated with the gene expression in BC and displayed the possibility of using the features to predict clinical receptors and PAM50 subtypes and to indicate BC prognosis.https://www.frontiersin.org/articles/10.3389/fonc.2022.943326/fullbreast cancerradiogenomicsradiomicsPAM50 subtypesDCE-MRImachine learning
spellingShingle Wenlong Ming
Yanhui Zhu
Yunfei Bai
Wanjun Gu
Wanjun Gu
Fuyu Li
Zixi Hu
Tiansong Xia
Zuolei Dai
Xiafei Yu
Huamei Li
Yu Gu
Shaoxun Yuan
Rongxin Zhang
Haitao Li
Wenyong Zhu
Jianing Ding
Xiao Sun
Yun Liu
Hongde Liu
Xiaoan Liu
Radiogenomics analysis reveals the associations of dynamic contrast-enhanced–MRI features with gene expression characteristics, PAM50 subtypes, and prognosis of breast cancer
Frontiers in Oncology
breast cancer
radiogenomics
radiomics
PAM50 subtypes
DCE-MRI
machine learning
title Radiogenomics analysis reveals the associations of dynamic contrast-enhanced–MRI features with gene expression characteristics, PAM50 subtypes, and prognosis of breast cancer
title_full Radiogenomics analysis reveals the associations of dynamic contrast-enhanced–MRI features with gene expression characteristics, PAM50 subtypes, and prognosis of breast cancer
title_fullStr Radiogenomics analysis reveals the associations of dynamic contrast-enhanced–MRI features with gene expression characteristics, PAM50 subtypes, and prognosis of breast cancer
title_full_unstemmed Radiogenomics analysis reveals the associations of dynamic contrast-enhanced–MRI features with gene expression characteristics, PAM50 subtypes, and prognosis of breast cancer
title_short Radiogenomics analysis reveals the associations of dynamic contrast-enhanced–MRI features with gene expression characteristics, PAM50 subtypes, and prognosis of breast cancer
title_sort radiogenomics analysis reveals the associations of dynamic contrast enhanced mri features with gene expression characteristics pam50 subtypes and prognosis of breast cancer
topic breast cancer
radiogenomics
radiomics
PAM50 subtypes
DCE-MRI
machine learning
url https://www.frontiersin.org/articles/10.3389/fonc.2022.943326/full
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