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从间充质-上皮转化角度看肝细胞癌的一种新表达特征与预后、临床病理特征、免疫细胞浸润、化疗疗效及免疫抑制分子的关系

A Novel Expression Signature from the Perspective of Mesenchymal-Epithelial Transition for Hepatocellular Carcinoma with Regard to Prognosis, Clinicopathological Features, Immune Cell Infiltration, Chemotherapeutic Efficacy, and Immunosuppressive Molecules.

作者信息

Xu Lijun, Zheng Qing

机构信息

Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Shanghai Institute of Digestive Disease, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine Shanghai Jiao Tong University, 160# Pu Jian Ave, Shanghai 200127, China.

出版信息

J Oncol. 2021 Jul 28;2021:5033416. doi: 10.1155/2021/5033416. eCollection 2021.

Abstract

PURPOSE

Mesenchymal-epithelial transition (MET), a reverse biological process to epithelial-mesenchymal transition (EMT), is involved in tumor metastasis and invasion. However, the role of MET-related genes (MRGs) in hepatocellular carcinoma (HCC) prognosis remains unclear.

METHODS

In this research, we obtained MRGs data and clinical information from public databases. In the TCGA dataset, a prognostic signature for HCC was constructed by the least absolute shrinkage and selection operator (LASSO) method and externally verified using the ICGC dataset.

RESULTS

There were 148 differentially expressed MRGs (DEMRGs), out of which 37 MRGs were found associated with overall survival (OS) in the univariate Cox analysis. A novel signature integrating of 5 MRGs was constructed, which split patients into high- and low-risk groups. Kaplan-Meier analysis revealed that high-risk patients had unfavorable OS than those low-risk counterparts. Receiver operating characteristic curve (ROC) showed great performance of this signature in predictive ability. Multivariate Cox analysis confirmed that this signature could independently predict HCC prognosis. The analysis of immune cell infiltration demonstrated that immune status varied differently between high- and low-risk groups. The analysis of clinicopathological characteristics suggested that tumor grade, clinical stage, and T stage were different between risk groups. The analysis between this signature and chemotherapeutic efficacy and immunosuppressive molecules indicated that this signature could serve as a promising predictor.

CONCLUSIONS

In conclusion, we constructed and verified a novel signature from the perspective of MET, which was significantly associated with HCC prognosis, clinicopathological features, immune status, chemotherapeutic efficacy, and immunosuppressive biomarkers.

摘要

目的

间充质-上皮转化(MET)是上皮-间充质转化(EMT)的逆向生物学过程,参与肿瘤转移和侵袭。然而,MET相关基因(MRGs)在肝细胞癌(HCC)预后中的作用仍不清楚。

方法

在本研究中,我们从公共数据库中获取了MRGs数据和临床信息。在TCGA数据集中,通过最小绝对收缩和选择算子(LASSO)方法构建了HCC的预后特征,并使用ICGC数据集进行外部验证。

结果

共有148个差异表达的MRGs(DEMRGs),其中37个MRGs在单变量Cox分析中与总生存期(OS)相关。构建了一个整合5个MRGs的新特征,将患者分为高风险组和低风险组。Kaplan-Meier分析显示,高风险患者的OS比低风险患者差。受试者工作特征曲线(ROC)显示该特征具有良好的预测能力。多变量Cox分析证实该特征可独立预测HCC预后。免疫细胞浸润分析表明,高风险组和低风险组的免疫状态存在差异。临床病理特征分析表明,风险组之间的肿瘤分级、临床分期和T分期不同。该特征与化疗疗效和免疫抑制分子之间的分析表明,该特征可作为一个有前景的预测指标。

结论

总之,我们从MET的角度构建并验证了一个新的特征,该特征与HCC预后、临床病理特征、免疫状态、化疗疗效和免疫抑制生物标志物显著相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ebd/8342179/e35e50b7501f/JO2021-5033416.001.jpg

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