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一种基于新型血管生成拟态的肝细胞癌预后模型的临床意义

Clinical Significance of a Novel Vasculogenic Mimicry-Based Prognostic Model in Hepatocellular Carcinoma.

作者信息

Zeng Yifan, Jiang Shuwen, Lou Zhuoqi, Chen Lin, Zhang Yongtao, Pan Liya, Shi Qingmiao, Ruan Bing

机构信息

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, 310003, China.

出版信息

Curr Med Chem. 2024 May 16. doi: 10.2174/0109298673298862240510073543.

Abstract

BACKGROUND

Vasculogenic mimicry, a novel neovascularization pattern of aggressive tumors, is associated with poor clinical outcomes.

OBJECTIVE

The aim of this research was to establish a new model, termed VC score, to predict the prognosis, Tumor Microenvironment (TME) components, and immunotherapeutic response in Hepatocellular Carcinoma (HCC).

METHODS

The expression data of the public databases were used to develop the prognostic model. Consensus clustering was performed to confirm the molecular subtypes with ideal clustering efficacy. The high- and low-risk groups were stratified utilizing the VC score. Various methodologies, including survival analysis, single-sample Gene Set Enrichment Analysis (ssGSEA), Tumor Immune Dysfunction and Exclusion scores (TIDE), Immunophenoscore (IPS), and nomogram, were utilized for verification of the model performance and to characterize the immune status of HCC tissues. GSEA was performed to mine functional pathway information.

RESULTS

The survival and immune characteristics varied between the three molecular subtypes. A five-gene signature (TPX2, CDC20, CFHR4, SPP1, and NQO1) was verified to function as an independent predictive factor for the prognosis of patients with HCC. The high-risk group exhibited lower Overall Survival (OS) rates and higher mortality rates in comparison to the low-risk group. Patients in the low-risk group were predicted to benefit from immune checkpoint inhibitor therapy and exhibit increased sensitivity to immunotherapy. Enrichment analysis revealed that signaling pathways linked to the cell cycle and DNA replication processes exhibited enrichment in the high-risk group.

CONCLUSIONS

The VC score holds the potential to establish individualized treatment plans and clinical management strategies for patients with HCC.

摘要

背景

血管生成拟态是侵袭性肿瘤一种新的血管生成模式,与不良临床预后相关。

目的

本研究旨在建立一种新模型,即VC评分,以预测肝细胞癌(HCC)的预后、肿瘤微环境(TME)成分及免疫治疗反应。

方法

利用公共数据库的表达数据建立预后模型。进行一致性聚类以确认具有理想聚类效果的分子亚型。利用VC评分对高、低风险组进行分层。采用多种方法,包括生存分析、单样本基因集富集分析(ssGSEA)、肿瘤免疫功能障碍与排除评分(TIDE)、免疫表型评分(IPS)和列线图,来验证模型性能并表征HCC组织的免疫状态。进行基因集富集分析(GSEA)以挖掘功能通路信息。

结果

三种分子亚型之间的生存和免疫特征各不相同。验证了一个五基因特征(TPX2、CDC20、CFHR4、SPP1和NQO1)可作为HCC患者预后的独立预测因子。与低风险组相比,高风险组的总生存期(OS)率较低,死亡率较高。预测低风险组患者将从免疫检查点抑制剂治疗中获益,并对免疫治疗表现出更高的敏感性。富集分析显示,与细胞周期和DNA复制过程相关的信号通路在高风险组中表现出富集。

结论

VC评分有潜力为HCC患者制定个体化治疗方案和临床管理策略。

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