A novel epithelial‐mesenchymal transition molecular signature predicts the oncological outcomes in colorectal cancer

Epithelial‐mesenchymal transition (EMT), a biological process involving the transformation of epithelial cells into mesenchymal cells, promotes tumour initiation and metastasis. The aim of this study was to construct an EMT molecular signature for predicting colorectal cancer (CRC) prognosis and eva...

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Published inJournal of cellular and molecular medicine Vol. 25; no. 7; pp. 3194 - 3204
Main Authors Shan, Zezhi, Wu, Wen, Yan, Xuebing, Yang, Yongzhi, Luo, Dakui, Liu, Qi, Li, Xinxiang, Goel, Ajay, Ma, Yanlei
Format Journal Article
LanguageEnglish
Published England John Wiley & Sons, Inc 01.04.2021
John Wiley and Sons Inc
Subjects
Clustering
Colorectal cancer
Colorectal carcinoma
Epithelial cells
epithelial‐Mesenchymal Transition
Gene expression
Growth factors
immunity
Lymph nodes
Medical prognosis
Mesenchyme
Metastases
Metastasis
Microenvironments
Multivariate analysis
Nomograms
Original
Patients
Principal components analysis
Prognosis
Regression analysis
risk score model
Software
Statistical analysis
Transcription factors
Tumor microenvironment
Tumors
colorectal cancer
immunity
risk score model
prognosis
epithelial-Mesenchymal Transition
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Abstract Epithelial‐mesenchymal transition (EMT), a biological process involving the transformation of epithelial cells into mesenchymal cells, promotes tumour initiation and metastasis. The aim of this study was to construct an EMT molecular signature for predicting colorectal cancer (CRC) prognosis and evaluate the efficacy of the model. The risk scoring system, constructed by log‐rank test and multivariate Cox regression analysis according to EMT‐related gene expression in CRC patients from TCGA database, demonstrated the highest correlation with prognosis compared with other parameters in CRC patients. The risk scores were significantly correlated with more lymph node metastasis, distal metastasis and advanced clinical stage of CRC. The model was further successfully validated in two independent external cohorts from GEO database. Furthermore, we developed a nomogram to integrate the EMT signature with the pathological stage of CRC, which was found to perform well in predicting the overall survival. Additionally, this risk scoring model was found to be associated with immune cell infiltration, implying a potential role of EMT involved in immunity regulation in tumour microenvironment. Taken together, our novel EMT molecular model may be useful in identifying high‐risk patients who need an intensive follow‐up and more aggressive therapy, finally contributing to more precise individualized therapeutic strategies.
AbstractList Epithelial‐mesenchymal transition (EMT), a biological process involving the transformation of epithelial cells into mesenchymal cells, promotes tumour initiation and metastasis. The aim of this study was to construct an EMT molecular signature for predicting colorectal cancer (CRC) prognosis and evaluate the efficacy of the model. The risk scoring system, constructed by log‐rank test and multivariate Cox regression analysis according to EMT‐related gene expression in CRC patients from TCGA database, demonstrated the highest correlation with prognosis compared with other parameters in CRC patients. The risk scores were significantly correlated with more lymph node metastasis, distal metastasis and advanced clinical stage of CRC. The model was further successfully validated in two independent external cohorts from GEO database. Furthermore, we developed a nomogram to integrate the EMT signature with the pathological stage of CRC, which was found to perform well in predicting the overall survival. Additionally, this risk scoring model was found to be associated with immune cell infiltration, implying a potential role of EMT involved in immunity regulation in tumour microenvironment. Taken together, our novel EMT molecular model may be useful in identifying high‐risk patients who need an intensive follow‐up and more aggressive therapy, finally contributing to more precise individualized therapeutic strategies.
Epithelial-mesenchymal transition (EMT), a biological process involving the transformation of epithelial cells into mesenchymal cells, promotes tumour initiation and metastasis. The aim of this study was to construct an EMT molecular signature for predicting colorectal cancer (CRC) prognosis and evaluate the efficacy of the model. The risk scoring system, constructed by log-rank test and multivariate Cox regression analysis according to EMT-related gene expression in CRC patients from TCGA database, demonstrated the highest correlation with prognosis compared with other parameters in CRC patients. The risk scores were significantly correlated with more lymph node metastasis, distal metastasis and advanced clinical stage of CRC. The model was further successfully validated in two independent external cohorts from GEO database. Furthermore, we developed a nomogram to integrate the EMT signature with the pathological stage of CRC, which was found to perform well in predicting the overall survival. Additionally, this risk scoring model was found to be associated with immune cell infiltration, implying a potential role of EMT involved in immunity regulation in tumour microenvironment. Taken together, our novel EMT molecular model may be useful in identifying high-risk patients who need an intensive follow-up and more aggressive therapy, finally contributing to more precise individualized therapeutic strategies.Epithelial-mesenchymal transition (EMT), a biological process involving the transformation of epithelial cells into mesenchymal cells, promotes tumour initiation and metastasis. The aim of this study was to construct an EMT molecular signature for predicting colorectal cancer (CRC) prognosis and evaluate the efficacy of the model. The risk scoring system, constructed by log-rank test and multivariate Cox regression analysis according to EMT-related gene expression in CRC patients from TCGA database, demonstrated the highest correlation with prognosis compared with other parameters in CRC patients. The risk scores were significantly correlated with more lymph node metastasis, distal metastasis and advanced clinical stage of CRC. The model was further successfully validated in two independent external cohorts from GEO database. Furthermore, we developed a nomogram to integrate the EMT signature with the pathological stage of CRC, which was found to perform well in predicting the overall survival. Additionally, this risk scoring model was found to be associated with immune cell infiltration, implying a potential role of EMT involved in immunity regulation in tumour microenvironment. Taken together, our novel EMT molecular model may be useful in identifying high-risk patients who need an intensive follow-up and more aggressive therapy, finally contributing to more precise individualized therapeutic strategies.
Author Li, Xinxiang
Yan, Xuebing
Shan, Zezhi
Luo, Dakui
Ma, Yanlei
Yang, Yongzhi
Goel, Ajay
Wu, Wen
Liu, Qi
AuthorAffiliation 1 Department of Colorectal Surgery Fudan University Shanghai Cancer Center Shanghai China
4 Department of Oncology the Affiliated Hospital of Yangzhou University Yangzhou University Yangzhou China
5 Department of Molecular Diagnostics and Experimental Therapeutics Beckman Research Institute of City of Hope Comprehensive Cancer Center Duarte CA USA
2 Department of Oncology Shanghai Medical College Fudan University Shanghai China
3 Department of Surgery Shanghai Pudong Hospital (Fudan University Pudong Medical Center) Shanghai China
AuthorAffiliation_xml – name: 4 Department of Oncology the Affiliated Hospital of Yangzhou University Yangzhou University Yangzhou China
– name: 3 Department of Surgery Shanghai Pudong Hospital (Fudan University Pudong Medical Center) Shanghai China
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– name: 5 Department of Molecular Diagnostics and Experimental Therapeutics Beckman Research Institute of City of Hope Comprehensive Cancer Center Duarte CA USA
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Keywords colorectal cancer
immunity
risk score model
prognosis
epithelial-Mesenchymal Transition
Language English
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This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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Notes Zezhi Shan, Wen Wu, Xuebing Yan and Yongzhi Yang contributed equally to this work.
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Snippet Epithelial‐mesenchymal transition (EMT), a biological process involving the transformation of epithelial cells into mesenchymal cells, promotes tumour...
Epithelial-mesenchymal transition (EMT), a biological process involving the transformation of epithelial cells into mesenchymal cells, promotes tumour...
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SubjectTerms Clustering
Colorectal cancer
Colorectal carcinoma
Epithelial cells
epithelial‐Mesenchymal Transition
Gene expression
Growth factors
immunity
Lymph nodes
Medical prognosis
Mesenchyme
Metastases
Metastasis
Microenvironments
Multivariate analysis
Nomograms
Original
Patients
Principal components analysis
Prognosis
Regression analysis
risk score model
Software
Statistical analysis
Transcription factors
Tumor microenvironment
Tumors
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Title A novel epithelial‐mesenchymal transition molecular signature predicts the oncological outcomes in colorectal cancer
URI https://onlinelibrary.wiley.com/doi/abs/10.1111%2Fjcmm.16387
https://www.ncbi.nlm.nih.gov/pubmed/33660944
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Volume 25
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