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A novel epithelial-mesenchymal transition molecular signature predicts the oncological outcomes in colorectal cancer |
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| Authors: | Zezhi Shan Wen Wu Xuebing Yan Yongzhi Yang Dakui Luo Qi Liu Xinxiang Li Ajay Goel Yanlei Ma |
| Institution: | 1. Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China Contribution: Conceptualization (lead), Data curation (lead), Formal analysis (lead), Methodology (lead), Resources (lead), Software (lead), Validation (lead), Writing - original draft (lead);2. Department of Surgery, Shanghai Pudong Hospital (Fudan University Pudong Medical Center), Shanghai, China Contribution: Formal analysis (equal), Methodology (equal);3. Department of Oncology, the Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China Contribution: Data curation (equal), Formal analysis (equal), Methodology (equal), Writing - original draft (equal);4. Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Project administration (equal), Supervision (lead), Writing - original draft (equal);5. Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China Contribution: Data curation (equal), Methodology (equal), Visualization (equal);6. Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China;7. Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA, USA |
| 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. |
| Keywords: | colorectal cancer epithelial-Mesenchymal Transition immunity prognosis risk score model |