• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

肝细胞癌中DNA甲基化调节因子相关分子模式与肿瘤免疫格局

DNA methylation regulators-related molecular patterns and tumor immune landscape in hepatocellular carcinoma.

作者信息

Song Dingli, Zhou Zhenyu, Wu Jie, Wei Tao, Zhao Guang, Ren Hong, Zhang Boxiang

机构信息

Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.

出版信息

Front Oncol. 2022 Aug 26;12:877817. doi: 10.3389/fonc.2022.877817. eCollection 2022.

DOI:10.3389/fonc.2022.877817
PMID:36091162
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9459088/
Abstract

Increasing evidence showed that the dysregulation of DNA methylation regulators is a decisive feature of almost all cancer types and affects tumor progressions. However, few studies focused on the underlying influences of DNA methylation regulators-related genes (DMRegs) in immune cell-infiltration characteristics, tumor microenvironment (TME) and immunotherapy in HCC patients. In our study, the alterations of DNA methylation regulators modification patterns (DMRPs) were clustered from hepatocellular carcinoma (HCC) samples based on the expression of DNA methylation regulators as well as genetic and transcriptional features. In addition, based on molecular identification of three distinct molecular subtypes, we found that different DMRPs alterations were related to different clinicopathological characteristics, prognosis, and immune cells infiltration features. Moreover, we constructed and validated a DNA methylation regulators-related genes score (DMRegs_score) to predict the survival of HCC patients. A high DMRegs _score, which was characterized by more TP53 wild mutation, high expression of PD-1, CTLA-4, and remarkable immunity activation, was indicative of poor prognosis. Furthermore, we validated the expression of eight genes which were used for the prognostic signature in this risk score by RT-qPCR using tissues from our center. More importantly, DMRegs_score was highly correlated with targeted drug sensitivity. Additionally, we developed a highly accurate scoring system that could be used to improve the clinical applicability of DMRegs _score. In conclusion, these findings may contribute to a better understanding of DNA methylation regulators and provide new strategies for evaluating prognosis and developing more effective combination therapy for HCC patients.

摘要

越来越多的证据表明，DNA甲基化调节因子的失调是几乎所有癌症类型的决定性特征，并影响肿瘤进展。然而，很少有研究关注DNA甲基化调节因子相关基因（DMRegs）对肝癌患者免疫细胞浸润特征、肿瘤微环境（TME）和免疫治疗的潜在影响。在我们的研究中，基于DNA甲基化调节因子的表达以及基因和转录特征，从肝细胞癌（HCC）样本中聚类出DNA甲基化调节因子修饰模式（DMRPs）的改变。此外，基于对三种不同分子亚型的分子鉴定，我们发现不同的DMRPs改变与不同的临床病理特征、预后和免疫细胞浸润特征相关。此外，我们构建并验证了一个DNA甲基化调节因子相关基因评分（DMRegs_score）来预测HCC患者的生存情况。高DMRegs_score以更多的TP53野生型突变、PD-1和CTLA-4的高表达以及显著的免疫激活为特征，预示着预后不良。此外，我们使用来自我们中心的组织通过RT-qPCR验证了用于该风险评分预后特征的八个基因的表达。更重要的是，DMRegs_score与靶向药物敏感性高度相关。此外，我们开发了一个高度准确的评分系统，可用于提高DMRegs_score的临床适用性。总之，这些发现可能有助于更好地理解DNA甲基化调节因子，并为评估HCC患者的预后和开发更有效的联合治疗提供新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbd/9459088/400fadd589e4/fonc-12-877817-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbd/9459088/c0e61f0b326b/fonc-12-877817-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbd/9459088/c9fd8e3c2cec/fonc-12-877817-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbd/9459088/95f2ba4173f4/fonc-12-877817-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbd/9459088/88958bf0a2f4/fonc-12-877817-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbd/9459088/dbdec3c94bd5/fonc-12-877817-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbd/9459088/658481ed9153/fonc-12-877817-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbd/9459088/1aada81ece6e/fonc-12-877817-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbd/9459088/14748bcf005b/fonc-12-877817-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbd/9459088/9d2dabdbaedf/fonc-12-877817-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbd/9459088/211eefa32370/fonc-12-877817-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbd/9459088/575885d2b4de/fonc-12-877817-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbd/9459088/400fadd589e4/fonc-12-877817-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbd/9459088/c0e61f0b326b/fonc-12-877817-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbd/9459088/c9fd8e3c2cec/fonc-12-877817-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbd/9459088/95f2ba4173f4/fonc-12-877817-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbd/9459088/88958bf0a2f4/fonc-12-877817-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbd/9459088/dbdec3c94bd5/fonc-12-877817-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbd/9459088/658481ed9153/fonc-12-877817-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbd/9459088/1aada81ece6e/fonc-12-877817-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbd/9459088/14748bcf005b/fonc-12-877817-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbd/9459088/9d2dabdbaedf/fonc-12-877817-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbd/9459088/211eefa32370/fonc-12-877817-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbd/9459088/575885d2b4de/fonc-12-877817-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbd/9459088/400fadd589e4/fonc-12-877817-g012.jpg

相似文献

1
DNA methylation regulators-related molecular patterns and tumor immune landscape in hepatocellular carcinoma.肝细胞癌中DNA甲基化调节因子相关分子模式与肿瘤免疫格局
Front Oncol. 2022 Aug 26;12:877817. doi: 10.3389/fonc.2022.877817. eCollection 2022.
2
m6A regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in hepatocellular carcinoma.m6A 调节子介导的甲基化修饰模式及肝癌肿瘤微环境浸润特征
Aging (Albany NY). 2021 Aug 30;13(16):20698-20715. doi: 10.18632/aging.203456.
3
Integrated investigation of the clinical implications and targeted landscape for RNA methylation modifications in hepatocellular carcinoma.肝细胞癌中 RNA 甲基化修饰的临床意义及靶向景观的综合研究。
Eur J Med Res. 2023 Jan 27;28(1):46. doi: 10.1186/s40001-023-01016-7.
4
DNA methylation regulator-mediated modification pattern defines tumor microenvironment immune infiltration landscape in colon cancer.DNA甲基化调节因子介导的修饰模式定义了结肠癌肿瘤微环境免疫浸润格局。
Front Genet. 2022 Oct 6;13:1008644. doi: 10.3389/fgene.2022.1008644. eCollection 2022.
5
Comprehensive characterization of m6A methylation and its impact on prognosis, genome instability, and tumor microenvironment in hepatocellular carcinoma.全面描述 m6A 甲基化及其对肝细胞癌预后、基因组不稳定性和肿瘤微环境的影响。
BMC Med Genomics. 2022 Mar 8;15(1):53. doi: 10.1186/s12920-022-01207-x.
6
Comprehensive Analysis of PD-L1 Expression, Immune Infiltrates, and m6A RNA Methylation Regulators in Esophageal Squamous Cell Carcinoma.食管鳞癌中 PD-L1 表达、免疫浸润与 m6A RNA 甲基化调控因子的综合分析
Front Immunol. 2021 May 12;12:669750. doi: 10.3389/fimmu.2021.669750. eCollection 2021.
7
Characterization of mA RNA Methylation Regulators Predicts Survival and Immunotherapy in Lung Adenocarcinoma.mA RNA 甲基化调控因子的特征可预测肺腺癌的生存和免疫治疗反应。
Front Immunol. 2021 Dec 17;12:782551. doi: 10.3389/fimmu.2021.782551. eCollection 2021.
8
Molecular subtypes, prognostic and immunotherapeutic relevant gene signatures mediated by DNA methylation regulators in hepatocellular carcinoma.肝细胞癌中 DNA 甲基化调控因子介导的分子亚型、预后和免疫治疗相关基因特征。
Aging (Albany NY). 2022 Jun 30;14(12):5271-5291. doi: 10.18632/aging.204155.
9
Identification and Validation of a Novel Tumor Microenvironment-Related Prognostic Signature of Patients With Hepatocellular Carcinoma.肝细胞癌患者一种新型肿瘤微环境相关预后特征的鉴定与验证
Front Mol Biosci. 2022 Jun 30;9:917839. doi: 10.3389/fmolb.2022.917839. eCollection 2022.
10
A Novel m1A-Score Model Correlated With the Immune Microenvironment Predicts Prognosis in Hepatocellular Carcinoma.一种与免疫微环境相关的新型 m1A 评分模型预测肝细胞癌的预后。
Front Immunol. 2022 Mar 24;13:805967. doi: 10.3389/fimmu.2022.805967. eCollection 2022.

引用本文的文献

1
Exploring the epigenetic mechanisms of recurrent pregnancy loss: from genetic predisposition to environmental influences.探索复发性流产的表观遗传机制：从遗传易感性到环境影响。
J Assist Reprod Genet. 2025 Aug 22. doi: 10.1007/s10815-025-03603-5.
2
New insights into N6-methyladenosine in hepatocellular carcinoma immunotherapy.肝细胞癌免疫治疗中N6-甲基腺苷的新见解。
Front Immunol. 2025 Jan 22;16:1533940. doi: 10.3389/fimmu.2025.1533940. eCollection 2025.
3
Development of a prognostic model for early-stage gastric cancer-related DNA methylation-driven genes and analysis of immune landscape.

本文引用的文献

1
mTOR-Mediated Regulation of Immune Responses in Cancer and Tumor Microenvironment.mTOR 介导的癌症和肿瘤微环境中免疫反应的调节。
Front Immunol. 2022 Feb 18;12:774103. doi: 10.3389/fimmu.2021.774103. eCollection 2021.
2
Diagnosis and prognosis models for hepatocellular carcinoma patient's management based on tumor mutation burden.基于肿瘤突变负荷的肝细胞癌患者管理的诊断和预后模型。
J Adv Res. 2021 Feb 9;33:153-165. doi: 10.1016/j.jare.2021.01.018. eCollection 2021 Nov.
3
Integrative Characterization of Immune-relevant Genes in Hepatocellular Carcinoma.
早期胃癌相关DNA甲基化驱动基因的预后模型开发及免疫格局分析
Front Mol Biosci. 2024 Oct 30;11:1455890. doi: 10.3389/fmolb.2024.1455890. eCollection 2024.
4
Application of methylation in the diagnosis of ankylosing spondylitis.甲基化在强直性脊柱炎诊断中的应用。
Clin Rheumatol. 2024 Oct;43(10):3073-3082. doi: 10.1007/s10067-024-07113-0. Epub 2024 Aug 21.
5
Research Progress on the Role of Epigenetic Methylation Modification in Hepatocellular Carcinoma.表观遗传甲基化修饰在肝细胞癌中作用的研究进展
J Hepatocell Carcinoma. 2024 Jun 17;11:1143-1156. doi: 10.2147/JHC.S458734. eCollection 2024.
6
From Reductionistic Approach to Systems Immunology Approach for the Understanding of Tumor Microenvironment.从还原论方法到系统免疫学方法理解肿瘤微环境。
Int J Mol Sci. 2023 Jul 28;24(15):12086. doi: 10.3390/ijms241512086.
7
Role of Plasma methylated SEPT9 for Predicting Microvascular Invasion and Tumor Proliferation in Hepatocellular Carcinoma.血浆 SEPT9 甲基化在预测肝细胞癌微血管侵犯和肿瘤增殖中的作用。
Technol Cancer Res Treat. 2022 Jan-Dec;21:15330338221144510. doi: 10.1177/15330338221144510.
8
Tumour-infiltrating lymphocytes: from prognosis to treatment selection.肿瘤浸润淋巴细胞：从预后到治疗选择。
Br J Cancer. 2023 Feb;128(3):451-458. doi: 10.1038/s41416-022-02119-4. Epub 2022 Dec 23.
肝细胞癌中免疫相关基因的综合表征
J Clin Transl Hepatol. 2021 Jun 28;9(3):301-314. doi: 10.14218/JCTH.2020.00132. Epub 2021 Mar 8.
4
DNA methylation regulator-mediated modification patterns and tumor microenvironment characterization in gastric cancer.DNA甲基化调节因子介导的胃癌修饰模式及肿瘤微环境特征
Mol Ther Nucleic Acids. 2021 Apr 3;24:695-710. doi: 10.1016/j.omtn.2021.03.023. eCollection 2021 Jun 4.
5
Pembrolizumab plus cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma: an open-label, multi-arm, non-randomised, multicentre, phase 2 trial.帕博利珠单抗联合西妥昔单抗治疗复发性或转移性头颈部鳞状细胞癌患者的开放标签、多臂、非随机、多中心、2 期临床试验。
Lancet Oncol. 2021 Jun;22(6):883-892. doi: 10.1016/S1470-2045(21)00136-4. Epub 2021 May 11.
6
Ipilimumab alone or ipilimumab plus anti-PD-1 therapy in patients with metastatic melanoma resistant to anti-PD-(L)1 monotherapy: a multicentre, retrospective, cohort study.伊匹木单抗单药治疗或伊匹木单抗联合抗PD-1治疗转移性黑色素瘤患者对抗PD-(L)1单药治疗耐药：一项多中心、回顾性队列研究。
Lancet Oncol. 2021 Jun;22(6):836-847. doi: 10.1016/S1470-2045(21)00097-8. Epub 2021 May 11.
7
Emerging immune checkpoints in the tumor microenvironment: Implications for cancer immunotherapy.肿瘤微环境中的新兴免疫检查点：对癌症免疫治疗的影响。
Cancer Lett. 2021 Jul 28;511:68-76. doi: 10.1016/j.canlet.2021.04.021. Epub 2021 May 3.
8
Recent Advances and Future Prospects in Immune Checkpoint (ICI)-Based Combination Therapy for Advanced HCC.基于免疫检查点抑制剂（ICI）的晚期肝癌联合治疗的最新进展与未来展望
Cancers (Basel). 2021 Apr 18;13(8):1949. doi: 10.3390/cancers13081949.
9
Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.《全球癌症统计数据 2020：全球 185 个国家和地区 36 种癌症的发病率和死亡率估计》。
CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.
10
Hepatocellular carcinoma.肝细胞癌。
Nat Rev Dis Primers. 2021 Jan 21;7(1):6. doi: 10.1038/s41572-020-00240-3.