• 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

一种新型蛋白质组学方法用于检测循环核小体的表观遗传特征。

A novel proteomics approach to epigenetic profiling of circulating nucleosomes.

机构信息

Belgian Volition SRL, 22 Rue Phocas Lejeune, Parc Scientifique Crealys, 5032, Isnes, Belgium.

EpiQMAx GmbH, Am Klopferspitz 19, 82152, Planegg-Martinsried, Germany.

出版信息

Sci Rep. 2021 Mar 31;11(1):7256. doi: 10.1038/s41598-021-86630-3.

DOI:10.1038/s41598-021-86630-3
PMID:33790358
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8012598/
Abstract

Alteration of epigenetic modifications plays an important role in human cancer. Notably, the dysregulation of histone post-translational modifications (PTMs) has been associated with several cancers including colorectal cancer (CRC). However, the signature of histone PTMs on circulating nucleosomes is still not well described. We have developed a fast and robust enrichment method to isolate circulating nucleosomes from plasma for further downstream proteomic analysis. This method enabled us to quantify the global alterations of histone PTMs from 9 CRC patients and 9 healthy donors. Among 54 histone proteoforms identified and quantified in plasma samples, 13 histone PTMs were distinctive in CRC. Notably, methylation of histone H3K9 and H3K27, acetylation of histone H3 and citrullination of histone H2A1R3 were upregulated in plasma of CRC patients. A comparative analysis of paired samples identified 3 common histone PTMs in plasma and tumor tissue including the methylation and acetylation state of lysine 27 of histone H3. Moreover, we highlight for the first time that histone H2A1R3 citrulline is a modification upregulated in CRC patients. This new method presented herein allows the detection and quantification of histone variants and histone PTMs from circulating nucleosomes in plasma samples and could be used for biomarker discovery of cancer.

摘要

表观遗传修饰的改变在人类癌症中起着重要作用。值得注意的是，组蛋白翻译后修饰（PTMs）的失调与包括结直肠癌（CRC）在内的几种癌症有关。然而，循环核小体中组蛋白 PTM 的特征仍然描述得不够清楚。我们开发了一种快速而稳健的富集方法，从血浆中分离循环核小体，以进行进一步的下游蛋白质组学分析。该方法使我们能够从 9 名 CRC 患者和 9 名健康供体中定量检测组蛋白 PTM 的全局变化。在血浆样本中鉴定和定量的 54 种组蛋白蛋白中，有 13 种组蛋白 PTM 在 CRC 中具有特征性。值得注意的是，CRC 患者血浆中组蛋白 H3K9 和 H3K27 的甲基化、组蛋白 H3 的乙酰化和组蛋白 H2A1R3 的瓜氨酸化上调。配对样本的比较分析鉴定出了 3 种在血浆和肿瘤组织中共同的组蛋白 PTM，包括组蛋白 H3 赖氨酸 27 的甲基化和乙酰化状态。此外，我们首次强调组蛋白 H2A1R3 瓜氨酸是 CRC 患者中上调的一种修饰。本文提出的这种新方法允许从血浆样本中的循环核小体中检测和定量组蛋白变体和组蛋白 PTM，并可用于癌症的生物标志物发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b598/8012598/614dc30efccc/41598_2021_86630_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b598/8012598/f52097177be0/41598_2021_86630_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b598/8012598/73073b5e7430/41598_2021_86630_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b598/8012598/a3cf3a459969/41598_2021_86630_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b598/8012598/ae9af2a45969/41598_2021_86630_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b598/8012598/614dc30efccc/41598_2021_86630_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b598/8012598/f52097177be0/41598_2021_86630_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b598/8012598/73073b5e7430/41598_2021_86630_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b598/8012598/a3cf3a459969/41598_2021_86630_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b598/8012598/ae9af2a45969/41598_2021_86630_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b598/8012598/614dc30efccc/41598_2021_86630_Fig5_HTML.jpg

相似文献

1
A novel proteomics approach to epigenetic profiling of circulating nucleosomes.一种新型蛋白质组学方法用于检测循环核小体的表观遗传特征。
Sci Rep. 2021 Mar 31;11(1):7256. doi: 10.1038/s41598-021-86630-3.
2
Histone Methylation Marks on Circulating Nucleosomes as Novel Blood-Based Biomarker in Colorectal Cancer.循环核小体上的组蛋白甲基化标记作为结直肠癌新型血液生物标志物
Int J Mol Sci. 2015 Dec 11;16(12):29654-62. doi: 10.3390/ijms161226180.
3
Post-translational histone modifications in circulating nucleosomes as new biomarkers in colorectal cancer.循环核小体中的翻译后组蛋白修饰作为结直肠癌的新型生物标志物
In Vivo. 2014 May-Jun;28(3):287-92.
4
Epigenetic profiles of elevated cell free circulating H3.1 nucleosomes as potential biomarkers for non-Hodgkin lymphoma.高细胞游离循环 H3.1 核小体的表观遗传学特征可作为非霍奇金淋巴瘤的潜在生物标志物。
Sci Rep. 2023 Sep 28;13(1):16335. doi: 10.1038/s41598-023-43520-0.
5
Comparative analysis of histone H3 and H4 post-translational modifications of esophageal squamous cell carcinoma with different invasive capabilities.具有不同侵袭能力的食管鳞状细胞癌中组蛋白H3和H4翻译后修饰的比较分析
J Proteomics. 2015 Jan 1;112:180-9. doi: 10.1016/j.jprot.2014.09.004. Epub 2014 Sep 16.
6
SILAC-based proteomic analysis to dissect the "histone modification signature" of human breast cancer cells.基于 SILAC 的蛋白质组学分析解析人类乳腺癌细胞的“组蛋白修饰特征”。
Amino Acids. 2011 Jul;41(2):387-99. doi: 10.1007/s00726-010-0668-2. Epub 2010 Jul 9.
7
Combinations of histone post-translational modifications.组蛋白翻译后修饰的组合。
Biochem J. 2021 Feb 12;478(3):511-532. doi: 10.1042/BCJ20200170.
8
Sequence-specific histone methylation is detectable on circulating nucleosomes in plasma.在血浆中循环核小体上可检测到序列特异性组蛋白甲基化。
Clin Chem. 2008 Jul;54(7):1125-31. doi: 10.1373/clinchem.2007.101766. Epub 2008 May 16.
9
Quantitation of nucleosome acetylation and other histone posttranslational modifications using microscale NU-ELISA.使用微量NU-ELISA对核小体乙酰化和其他组蛋白翻译后修饰进行定量分析。
Methods Mol Biol. 2013;981:167-76. doi: 10.1007/978-1-62703-305-3_13.
10
Histone H3K4 and H3K36 Methylation Independently Recruit the NuA3 Histone Acetyltransferase in .组蛋白H3K4和H3K36甲基化分别招募NuA3组蛋白乙酰转移酶……（原文此处不完整）
Genetics. 2017 Mar;205(3):1113-1123. doi: 10.1534/genetics.116.199422. Epub 2017 Jan 20.

引用本文的文献

1
High-throughput epigenetic profiling immunoassays for accelerated disease research and clinical development.用于加速疾病研究和临床开发的高通量表观遗传学分析免疫测定法。
J Biol Chem. 2025 Jun 7;301(7):110352. doi: 10.1016/j.jbc.2025.110352.
2
Omics technologies as powerful approaches to unravel colorectal cancer complexity and improve its management.组学技术是揭示结直肠癌复杂性并改善其治疗的有力方法。
Mol Cells. 2025 May;48(5):100200. doi: 10.1016/j.mocell.2025.100200. Epub 2025 Feb 28.
3
Single-molecule systems for the detection and monitoring of plasma-circulating nucleosomes and oncoproteins in diffuse midline glioma.

本文引用的文献

1
Mass spectrometry-based characterization of histones in clinical samples: applications, progress, and challenges.基于质谱的临床样本组蛋白分析：应用、进展与挑战。
FEBS J. 2022 Mar;289(5):1191-1213. doi: 10.1111/febs.15707. Epub 2021 Jan 23.
2
Histone tail analysis reveals H3K36me2 and H4K16ac as epigenetic signatures of diffuse intrinsic pontine glioma.组蛋白尾部分析显示 H3K36me2 和 H4K16ac 是弥漫性内在脑桥胶质瘤的表观遗传特征。
J Exp Clin Cancer Res. 2020 Nov 25;39(1):261. doi: 10.1186/s13046-020-01773-x.
3
Profiling of Epigenetic Features in Clinical Samples Reveals Novel Widespread Changes in Cancer.
用于检测和监测弥漫性中线胶质瘤中血浆循环核小体和癌蛋白的单分子系统。
Cell Rep Med. 2025 Jan 21;6(1):101918. doi: 10.1016/j.xcrm.2024.101918. Epub 2025 Jan 13.
4
Back pain exercise therapy remodels human epigenetic profiles in buccal and human peripheral blood mononuclear cells: an exploratory study in young male participants.背痛运动疗法重塑颊黏膜和人外周血单个核细胞中的人类表观遗传谱：一项针对年轻男性参与者的探索性研究。
Front Sports Act Living. 2024 Oct 16;6:1393067. doi: 10.3389/fspor.2024.1393067. eCollection 2024.
5
Multi Omics Applications in Biological Systems.生物系统中的多组学应用
Curr Issues Mol Biol. 2024 Jun 11;46(6):5777-5793. doi: 10.3390/cimb46060345.
6
Epigenetic modifications of cfDNA in liquid biopsy for the cancer care continuum.用于癌症全程管理的液体活检中循环游离DNA的表观遗传修饰
Biomed J. 2025 Feb;48(1):100718. doi: 10.1016/j.bj.2024.100718. Epub 2024 Mar 23.
7
Use of tryptic peptide MALDI mass spectrometry imaging to identify the spatial proteomic landscape of colorectal cancer liver metastases.使用胰蛋白酶肽 MALDI 质谱成像技术鉴定结直肠癌肝转移的空间蛋白质组图谱。
Clin Exp Med. 2024 Mar 16;24(1):53. doi: 10.1007/s10238-024-01311-5.
8
Liquid Liver Biopsy for Disease Diagnosis and Prognosis.用于疾病诊断和预后的液体肝活检
J Clin Transl Hepatol. 2023 Dec 28;11(7):1520-1541. doi: 10.14218/JCTH.2023.00040. Epub 2023 Jul 27.
9
Mass Spectrometry-Based Proteomics: Analyses Related to Drug-Resistance and Disease Biomarkers.基于质谱的蛋白质组学：与药物耐药性和疾病生物标志物相关的分析。
Medicina (Kaunas). 2023 Sep 27;59(10):1722. doi: 10.3390/medicina59101722.
10
Epigenetic profiles of elevated cell free circulating H3.1 nucleosomes as potential biomarkers for non-Hodgkin lymphoma.高细胞游离循环 H3.1 核小体的表观遗传学特征可作为非霍奇金淋巴瘤的潜在生物标志物。
Sci Rep. 2023 Sep 28;13(1):16335. doi: 10.1038/s41598-023-43520-0.
临床样本中表观遗传特征分析揭示癌症中广泛存在的新变化。
Cancers (Basel). 2019 May 24;11(5):723. doi: 10.3390/cancers11050723.
4
Elevating H3K27me3 level sensitizes colorectal cancer to oxaliplatin.提高 H3K27me3 水平可使结直肠癌对奥沙利铂敏感。
J Mol Cell Biol. 2020 Feb 20;12(2):125-137. doi: 10.1093/jmcb/mjz032.
5
H3.3 K27M depletion increases differentiation and extends latency of diffuse intrinsic pontine glioma growth in vivo.H3.3 K27M 耗竭增加了弥漫性内在脑桥神经胶质瘤在体内的分化并延长了潜伏期。
Acta Neuropathol. 2019 Apr;137(4):637-655. doi: 10.1007/s00401-019-01975-4. Epub 2019 Feb 15.
6
Clinical epigenetics: seizing opportunities for translation.临床表观遗传学：抓住转化机遇。
Nat Rev Genet. 2019 Feb;20(2):109-127. doi: 10.1038/s41576-018-0074-2.
7
Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.全球癌症统计数据 2018：GLOBOCAN 对全球 185 个国家/地区 36 种癌症的发病率和死亡率的估计。
CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.
8
Stability of histone post-translational modifications in samples derived from liver tissue and primary hepatic cells.肝组织和原代肝细胞样本中组蛋白翻译后修饰的稳定性。
PLoS One. 2018 Sep 7;13(9):e0203351. doi: 10.1371/journal.pone.0203351. eCollection 2018.
9
Genetic and epigenetic alterations of colorectal cancer.结直肠癌的遗传和表观遗传改变。
Intest Res. 2018 Jul;16(3):327-337. doi: 10.5217/ir.2018.16.3.327. Epub 2018 Jul 27.
10
Detection of Histone Modification Dynamics during the Cell Cycle by MS-Based Proteomics.基于质谱的蛋白质组学检测细胞周期中的组蛋白修饰动态变化
Methods Mol Biol. 2018;1832:61-74. doi: 10.1007/978-1-4939-8663-7_4.