基于病因学的肝癌分子特征揭示了SQLE在免疫抑制微环境中的作用。

IF 2.3 4区 医学 Q3 ONCOLOGY
Kangkang Yu, Qisheng Zhong, Jubo Zhang, Chong Huang
{"title":"基于病因学的肝癌分子特征揭示了SQLE在免疫抑制微环境中的作用。","authors":"Kangkang Yu, Qisheng Zhong, Jubo Zhang, Chong Huang","doi":"10.2174/0115680096370558250514063841","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a kind of fatal cancer with a variety of risk factors. However, a pan-etiology molecular characterization of HCC has not been explored.</p><p><strong>Objective: </strong>The objective of this study is to explore etiology-specific features of HCC and im-prove our understanding of tumorigenesis, thereby revealing potential therapeutic targets.</p><p><strong>Methods: </strong>RNA-seq, genetic alteration, copy number alteration, and clinicopathological data of The Cancer Genome Atlas -Liver Hepatocellular Carcinoma cohort were downloaded and explored. Immune-related features and single-cell and spatial transcriptomic data were adopted and analyzed.</p><p><strong>Results: </strong>Etiology-based analyses revealed that HCC with different etiologies showed different clinical features, including gender composition, ethnic composition, clinical stage distribution, and survival. In addition, distinct genetic alterations, copy number alterations, and tumor microenvironment were observed in HCC patients with different etiologies. Significantly enhanced expression of squalene epoxidase (SQLE) was observed in viral hepatitis-related HCC and was associated with poor tumor grade and overall survival. Correlation analysis revealed a negative relationship between SQLE expression and anti-tumor immunity. Single-cell and spatial transcriptomics demonstrated that SQLE contributed to reduced T cell and NK cell infiltration while increasing macrophage and monocyte infiltration.</p><p><strong>Conclusion: </strong>The current study demonstrated that HCC has etiology-specific clinical features, genetic alteration, copy number alteration, and tumor microenvironment. Overexpression of SQLE in viral hepatitis-related HCC correlate with poor clinical outcome and may contribute to reduce T cell and NK cell infiltration while increased macrophage and monocyte infiltration, which lead to immunosuppressive microenvironment and can be an actionable target.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Etiology-based Molecular Characterization of Hepatocellular Carcinoma Reveals SQLE's Contribution to Immunosuppressive Microenvironment.\",\"authors\":\"Kangkang Yu, Qisheng Zhong, Jubo Zhang, Chong Huang\",\"doi\":\"10.2174/0115680096370558250514063841\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a kind of fatal cancer with a variety of risk factors. However, a pan-etiology molecular characterization of HCC has not been explored.</p><p><strong>Objective: </strong>The objective of this study is to explore etiology-specific features of HCC and im-prove our understanding of tumorigenesis, thereby revealing potential therapeutic targets.</p><p><strong>Methods: </strong>RNA-seq, genetic alteration, copy number alteration, and clinicopathological data of The Cancer Genome Atlas -Liver Hepatocellular Carcinoma cohort were downloaded and explored. Immune-related features and single-cell and spatial transcriptomic data were adopted and analyzed.</p><p><strong>Results: </strong>Etiology-based analyses revealed that HCC with different etiologies showed different clinical features, including gender composition, ethnic composition, clinical stage distribution, and survival. In addition, distinct genetic alterations, copy number alterations, and tumor microenvironment were observed in HCC patients with different etiologies. Significantly enhanced expression of squalene epoxidase (SQLE) was observed in viral hepatitis-related HCC and was associated with poor tumor grade and overall survival. Correlation analysis revealed a negative relationship between SQLE expression and anti-tumor immunity. Single-cell and spatial transcriptomics demonstrated that SQLE contributed to reduced T cell and NK cell infiltration while increasing macrophage and monocyte infiltration.</p><p><strong>Conclusion: </strong>The current study demonstrated that HCC has etiology-specific clinical features, genetic alteration, copy number alteration, and tumor microenvironment. Overexpression of SQLE in viral hepatitis-related HCC correlate with poor clinical outcome and may contribute to reduce T cell and NK cell infiltration while increased macrophage and monocyte infiltration, which lead to immunosuppressive microenvironment and can be an actionable target.</p>\",\"PeriodicalId\":10816,\"journal\":{\"name\":\"Current cancer drug targets\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2025-05-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current cancer drug targets\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/0115680096370558250514063841\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current cancer drug targets","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0115680096370558250514063841","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

背景:肝细胞癌(HCC)是一种具有多种危险因素的致死性癌症。然而,HCC的泛病因学分子特征尚未被探讨。目的:本研究的目的是探讨HCC的病因特异性特征,提高我们对肿瘤发生的认识,从而揭示潜在的治疗靶点。方法:下载肿瘤基因组图谱-肝癌队列的RNA-seq、遗传改变、拷贝数改变和临床病理数据。采用并分析免疫相关特征、单细胞和空间转录组数据。结果:基于病因学的分析显示,不同病因的HCC表现出不同的临床特征,包括性别构成、民族构成、临床分期分布和生存期。此外,在不同病因的HCC患者中观察到不同的遗传改变、拷贝数改变和肿瘤微环境。在病毒性肝炎相关性HCC中观察到角鲨烯环氧化酶(SQLE)的表达显著增强,并与肿瘤分级差和总生存率相关。相关分析显示,SQLE表达与抗肿瘤免疫呈负相关。单细胞和空间转录组学表明,SQLE有助于减少T细胞和NK细胞的浸润,同时增加巨噬细胞和单核细胞的浸润。结论:目前的研究表明HCC具有病因特异性的临床特征、基因改变、拷贝数改变和肿瘤微环境。在病毒性肝炎相关性HCC中,SQLE过表达与临床预后差相关,可能导致T细胞和NK细胞浸润减少,巨噬细胞和单核细胞浸润增加,导致免疫抑制微环境,可能是一个可操作的靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Etiology-based Molecular Characterization of Hepatocellular Carcinoma Reveals SQLE's Contribution to Immunosuppressive Microenvironment.

Background: Hepatocellular carcinoma (HCC) is a kind of fatal cancer with a variety of risk factors. However, a pan-etiology molecular characterization of HCC has not been explored.

Objective: The objective of this study is to explore etiology-specific features of HCC and im-prove our understanding of tumorigenesis, thereby revealing potential therapeutic targets.

Methods: RNA-seq, genetic alteration, copy number alteration, and clinicopathological data of The Cancer Genome Atlas -Liver Hepatocellular Carcinoma cohort were downloaded and explored. Immune-related features and single-cell and spatial transcriptomic data were adopted and analyzed.

Results: Etiology-based analyses revealed that HCC with different etiologies showed different clinical features, including gender composition, ethnic composition, clinical stage distribution, and survival. In addition, distinct genetic alterations, copy number alterations, and tumor microenvironment were observed in HCC patients with different etiologies. Significantly enhanced expression of squalene epoxidase (SQLE) was observed in viral hepatitis-related HCC and was associated with poor tumor grade and overall survival. Correlation analysis revealed a negative relationship between SQLE expression and anti-tumor immunity. Single-cell and spatial transcriptomics demonstrated that SQLE contributed to reduced T cell and NK cell infiltration while increasing macrophage and monocyte infiltration.

Conclusion: The current study demonstrated that HCC has etiology-specific clinical features, genetic alteration, copy number alteration, and tumor microenvironment. Overexpression of SQLE in viral hepatitis-related HCC correlate with poor clinical outcome and may contribute to reduce T cell and NK cell infiltration while increased macrophage and monocyte infiltration, which lead to immunosuppressive microenvironment and can be an actionable target.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Current cancer drug targets
Current cancer drug targets 医学-肿瘤学
CiteScore
5.40
自引率
0.00%
发文量
105
审稿时长
1 months
期刊介绍: Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes and genes. Current Cancer Drug Targets publishes original research articles, letters, reviews / mini-reviews, drug clinical trial studies and guest edited thematic issues written by leaders in the field covering a range of current topics on drug targets involved in cancer. As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信