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坏死性凋亡相关基因特征鉴定肝细胞癌的分子亚型及潜在机制

Necroptosis-Related Genes Signatures Identified Molecular Subtypes and Underlying Mechanisms in Hepatocellular Carcinoma.

作者信息

Wei Jianguo, Hou Shuqian, Li Minhua, Yao Xiaofei, Wang Li, Zheng Zhen, Mo Haiqian, Chen Yu, Yuan Xiaolu

机构信息

Department of Pathology, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, China.

Department of Pathology, Maoming People's Hospital, Maoming, China.

出版信息

Front Oncol. 2022 Jul 13;12:875264. doi: 10.3389/fonc.2022.875264. eCollection 2022.

DOI:10.3389/fonc.2022.875264
PMID:35912224
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9326098/
Abstract

BACKGROUND

Although emerging evidence supports the relationship between necroptosis (NEC) related genes and hepatocellular carcinoma (HCC), the contribution of these necroptosis-related genes to the development, prognosis, and immunotherapy of HCC is unclear.

METHODS

The expression of genes and relevant clinical information were downloaded from TCGA-LIHC, LIRI-JP, GSE14520/NCI, GSE36376, GSE76427, GSE20140, GSE27150, and IMvigor210 datasets. Next, we used an unsupervised clustering method to assign the samples into phenotype clusters base on 15 necroptosis-related genes. Subsequently, we constructed a NEC score based on NEC phenotype-related prognostic genes to quantify the necroptosis related subtypes of individual patients.

RESULTS

We divided the samples into the high and low NEC score groups, and the high NEC score showed a poor prognosis. Simultaneously, NEC score is an effective and stable model and had a good performance in predicting the prognosis of HCC patients. A high NEC score was characterized by activation of the stroma and increased levels of immune infiltration. A high NEC score was also related to low expression of immune checkpoint molecules (PD-1/PD-L1). Importantly, the established NEC score would contribute to predicting the response to anti-PD-1/L1 immunotherapy.

CONCLUSIONS

Our study provide a comprehensive analysis of necroptosis-related genes in HCC. Stratification based on the NEC score may enable HCC patients to benefit more from immunotherapy and help identify new cancer treatment strategies.

摘要

背景

尽管新出现的证据支持坏死性凋亡（NEC）相关基因与肝细胞癌（HCC）之间的关系，但这些坏死性凋亡相关基因对HCC的发生、预后和免疫治疗的贡献尚不清楚。

方法

从TCGA-LIHC、LIRI-JP、GSE14520/NCI、GSE36376、GSE76427、GSE20140、GSE27150和IMvigor210数据集中下载基因表达及相关临床信息。接下来，我们使用无监督聚类方法，基于15个坏死性凋亡相关基因将样本分配到表型簇中。随后，我们基于与NEC表型相关的预后基因构建了一个NEC评分，以量化个体患者的坏死性凋亡相关亚型。

结果

我们将样本分为高NEC评分组和低NEC评分组，高NEC评分显示预后较差。同时，NEC评分是一个有效且稳定的模型，在预测HCC患者预后方面表现良好。高NEC评分的特征是基质激活和免疫浸润水平增加。高NEC评分还与免疫检查点分子（PD-1/PD-L1）的低表达有关。重要的是，所建立的NEC评分有助于预测对抗PD-1/L1免疫治疗的反应。

结论

我们的研究对HCC中坏死性凋亡相关基因进行了全面分析。基于NEC评分的分层可能使HCC患者从免疫治疗中获益更多，并有助于确定新的癌症治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7459/9326098/e57d7aa47e8f/fonc-12-875264-g010.jpg
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