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一种新型上皮-间充质转化分子特征可预测结直肠癌的肿瘤学结局。

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

机构信息

Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

出版信息

J Cell Mol Med. 2021 Apr;25(7):3194-3204. doi: 10.1111/jcmm.16387. Epub 2021 Mar 4.

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.

摘要

上皮-间充质转化(EMT)是一种涉及上皮细胞向间充质细胞转化的生物学过程,促进肿瘤的起始和转移。本研究旨在构建 EMT 分子特征,以预测结直肠癌(CRC)的预后,并评估该模型的疗效。根据 TCGA 数据库中 CRC 患者的 EMT 相关基因表达,通过对数秩检验和多变量 Cox 回归分析构建的风险评分系统,与 CRC 患者的其他参数相比,与预后的相关性最高。风险评分与更多的淋巴结转移、远处转移和 CRC 的晚期临床分期显著相关。该模型在 GEO 数据库中的两个独立外部队列中也得到了成功验证。此外,我们开发了一个列线图,将 EMT 特征与 CRC 的病理分期相结合,该列线图在预测总生存期方面表现良好。此外,该风险评分模型与免疫细胞浸润相关,提示 EMT 在肿瘤微环境中的免疫调节中可能发挥作用。总之,我们的新型 EMT 分子模型可能有助于识别需要强化随访和更积极治疗的高危患者,最终有助于制定更精确的个体化治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/670a/8034457/a98dd2038977/JCMM-25-3194-g003.jpg

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