Genes & Diseases最新文献_第5页

DNA damage-induced nuclear STING translocation orchestrates innate immune activation and chromatin remodeling DNA损伤诱导的核STING易位协调先天免疫激活和染色质重塑

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2025-09-09 DOI: 10.1016/j.gendis.2025.101851

Yihao Wang , Zan Shen , Lingjie Li , Jianfeng Shen

引用次数: 0

Transcriptional rewiring by enhancer methylation in CBFA2T3-GLIS2–driven pediatric acute megakaryoblastic leukemia cbfa2t3 - glis2驱动的儿童急性巨核细胞白血病中增强子甲基化的转录重接线

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2025-09-06 DOI: 10.1016/j.gendis.2025.101843

Samrat Roy Choudhury , Akhilesh Kaushal , Pritam Biswas , Cory Padilla , Jay F. Sarthy , Arundhati Chavan , Giselle Almeida Gonzalez , Soheil Meshinchi , Jason E. Farrar

Resistance to chemotherapy and subsequent relapse remain the primary challenge in pediatric acute myeloid leukemia (pAML), particularly in CBFA2T3-GLIS2 (C/G) fusion-positive acute megakaryoblastic leukemia. Here we demonstrate that the C/G fusion drives extensive DNA methylation changes and oncogenic enhancer activation at cis-regulatory elements (CREs), reshaping gene expression. This multi-omics analysis reveals a distinct hypermethylation pattern at promoters of up-regulated genes in C/G⁺ pAML across patient samples (n = 24) and representative cell lines, notably enriched in adhesion-related, TGFβ, or Wnt signaling pathways. Hypermethylated regions adjacent to transcription start sites (TSS) maintain open chromatin with H3K27ac enrichment, supporting a mechanism of de novo chromatin looping and active transcription in a non-canonical manner. Additionally, C/G fusion binding near the DNA methyltransferase 3B (DNMT3B) promoter correlates with elevated DNMT3B expression, implicating its role in aberrant DNA methylation changes at CREs. This study elucidates the epigenetic mechanisms driving C/G⁺ pAML, showing how the fusion reshapes chromatin and DNA methylation landscapes by impacting the expression (and likely activity) of epigenetic modifiers like DNMT3B. Functionally, DNMT3B inhibition enhances apoptotic sensitivity to BCL2 blockade, indicating that targeting DNMT3B may overcome apoptotic resistance in C/G⁺ leukemic cells and offer a therapeutic strategy for this high-risk subtype.

化疗耐药性和随后的复发仍然是儿童急性髓性白血病（pAML）的主要挑战，特别是CBFA2T3-GLIS2 （C/G）融合阳性急性巨核细胞白血病。在这里，我们证明C/G融合驱动广泛的DNA甲基化变化和顺式调控元件（cre）的致癌增强子激活，重塑基因表达。这项多组学分析揭示了患者样本（n = 24）和代表性细胞系中C/G+ pAML上调基因启动子的明显高甲基化模式，特别是在粘附相关、TGFβ或Wnt信号通路中富集。转录起始位点（TSS）附近的高甲基化区域通过H3K27ac富集维持染色质开放，支持非规范方式的染色质新生环和主动转录机制。此外，DNA甲基转移酶3B （DNMT3B）启动子附近的C/G融合结合与DNMT3B表达升高相关，暗示其在CREs异常DNA甲基化变化中的作用。这项研究阐明了驱动C/G+ pAML的表观遗传机制，展示了融合如何通过影响DNMT3B等表观遗传修饰因子的表达（和可能的活性）来重塑染色质和DNA甲基化景观。在功能上，DNMT3B抑制增强了凋亡对BCL2阻断的敏感性，表明靶向DNMT3B可能克服C/G+白血病细胞的凋亡耐药，并为这种高风险亚型提供治疗策略。

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引用次数: 0

In vivo multiplexed modeling reveals diverse roles of the TBX2 subfamily and Egr1 in Kras-driven lung adenocarcinoma 体内多路建模揭示了TBX2亚家族和Egr1在kras驱动的肺腺癌中的不同作用

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2025-09-03 DOI: 10.1016/j.gendis.2025.101840

Athar Khalil , Trang Dinh , Meaghan Parks , Rebecca C. Obeng , Berkley Gryder , Adam Kresak , Yuxiang Wang , Jeff Maltas , Madeline Bedrock , Xiangzhen Wei , Zachary Faber , Mira Rahm , Jacob Scott , Thomas LaFramboise , Zhenghe Wang , Christopher McFarland

The TBX2 subfamily of T-box transcription factors (e.g., Tbx2, Tbx3, Tbx4, Tbx5) plays an essential role in lung development. Down-regulation of these genes in human lung adenocarcinoma suggests that these genes may be tumor-suppressive; however, because down-regulation appears to occur primarily via epigenetic change, it remains unclear if these changes causally drive tumor progression or are merely the consequence of upstream events. Herein, we developed the first multiplexed mouse model to study the impact of TBX2 subfamily loss, alongside associated signaling genes (Egr1, Chd2, Tnfaip3a, and Atf3) in Ras-driven lung cancer. Using tumor-barcoding with high-throughput barcode sequencing (TuBa-seq), a high-throughput tumor-barcoding system, we quantified the growth effects of these knockouts during early and late tumorigenesis. Chd2 knockout suppressed both tumor initiation and progression, whereas Tnfaip3 knockout enhanced tumor initiation and overall tumor growth. Tbx2 loss showed stage-specific effects on tumor development. Notably, Egr1 emerged as a strong tumor suppressor and its knockout resulted in approximately a fivefold increase in tumor size at 20 weeks (two-sample t-test, p < 0.05), exceeding the impact observed with Rb1 loss. Transcriptomic analyses of Egr1-deficient tumors suggested immune dysregulation, including heightened inflammation and potential markers of T cell exhaustion in the tumor microenvironment. These findings indicate that Egr1 may play a role in suppressing tumor growth through modulating immune dynamics, offering new insights into the interplay between tumor progression and immune regulation in lung adenocarcinoma.

T-box转录因子TBX2亚家族（如TBX2、Tbx3、Tbx4、Tbx5）在肺发育中起重要作用。这些基因在人肺腺癌中的下调表明这些基因可能具有肿瘤抑制作用；然而，由于下调似乎主要通过表观遗传变化发生，尚不清楚这些变化是导致肿瘤进展的原因还是仅仅是上游事件的结果。在此，我们建立了第一个多路小鼠模型来研究TBX2亚家族缺失以及相关信号基因（Egr1, Chd2， Tnfaip3a和Atf3）在ras驱动型肺癌中的影响。使用肿瘤条形码和高通量条形码测序（TuBa-seq），一种高通量肿瘤条形码系统，我们量化了这些敲除在肿瘤发生早期和晚期的生长效应。Chd2敲除抑制肿瘤的发生和进展，而Tnfaip3敲除增强肿瘤的发生和肿瘤的整体生长。Tbx2缺失对肿瘤的发展表现出阶段性的影响。值得注意的是，Egr1作为一种强大的肿瘤抑制因子出现，其敲除导致肿瘤大小在20周时增加约5倍（双样本t检验，p < 0.05），超过了Rb1缺失所观察到的影响。egr1缺陷肿瘤的转录组学分析表明免疫失调，包括肿瘤微环境中炎症加剧和T细胞衰竭的潜在标志物。这些发现表明，Egr1可能通过调节免疫动力学来抑制肿瘤生长，为肺腺癌肿瘤进展与免疫调节之间的相互作用提供了新的见解。

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引用次数: 0

Enhanced transcriptomic profiling of esophageal tissue through optimized PAXgene fixation protocols 通过优化PAXgene固定方案增强食管组织转录组谱分析

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2025-09-02 DOI: 10.1016/j.gendis.2025.101842

Fadi Charara , Louison Descampe , Ligia Craciun , Laurine Verset , Alexandre Spinette , Meriem Ennaji , Maarten Vander Kuylen , Calliope Maris , Pieter Demetter , Benjamin Beck

引用次数: 0

Targeting SUMOylation in glioblastoma: A novel avenue for therapy and biomarker discovery 胶质母细胞瘤的靶向sumo化：治疗和生物标志物发现的新途径

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2025-09-02 DOI: 10.1016/j.gendis.2025.101841

Wiktoria Dubanosow, Bartosz Lenda, Marta Żebrowska-Nawrocka, Dagmara Szmajda-Krygier, Rafał Świechowski, Ewa Balcerczak

SUMOylation, a post-translational protein modification, plays a crucial role in regulating various biological processes. Dysregulation of SUMOylation has been linked to glioblastoma progression, impacting key signaling pathways. This review summarizes the current knowledge on SUMOylation's role in glioma malignancy, highlighting its influence on cell cycle regulation, PKB/AKT signaling pathway, and microRNA expression. Our work identifies Ubc9 as a promising therapeutic target due to its role in enhancing SUMOylation, promoting glioblastoma aggressiveness, and facilitating tumor proliferation. Additionally, SAE1 correlates with glioblastoma grade and affects cell cycle regulators, while SUMOylation stabilizes CDK6, driving the G1/S transition. Targeting these pathways with inhibitors, such as topotecan and chlorogenic acid, may provide novel treatment strategies. Furthermore, SUMOylation-driven alterations in transcription factors and DNA repair mechanisms contribute to therapy resistance. Understanding these mechanisms could pave the way for innovative interventions in glioblastoma management.

SUMOylation是一种翻译后蛋白修饰，在调节多种生物过程中起着至关重要的作用。SUMOylation的失调与胶质母细胞瘤的进展有关，影响关键的信号通路。本文综述了SUMOylation在胶质瘤恶性肿瘤中的作用，重点介绍了其对细胞周期调节、PKB/AKT信号通路和microRNA表达的影响。我们的工作确定了Ubc9是一个有希望的治疗靶点，因为它在增强sumo化，促进胶质母细胞瘤侵袭性和促进肿瘤增殖中的作用。此外，SAE1与胶质母细胞瘤分级相关，影响细胞周期调节因子，而SUMOylation稳定CDK6，推动G1/S转变。用抑制剂，如拓扑替康和绿原酸靶向这些途径，可能提供新的治疗策略。此外，sumoyl化驱动的转录因子和DNA修复机制的改变有助于治疗耐药性。了解这些机制可以为胶质母细胞瘤治疗的创新干预铺平道路。

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引用次数: 0

Role of miR-101a in targeting Cox-2 to attenuate chondrocyte hypertrophic differentiation and osteoarthritis progression miR-101a在靶向Cox-2减轻软骨细胞肥厚分化和骨关节炎进展中的作用。

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2025-09-01 DOI: 10.1016/j.gendis.2025.101839

Rui Mi , Jinnan Chen , Tianxiang Zhu , Huiqin Bian , Rong Wei , Rushuang Deng , Tiaotiao Han , Qian Wang , Yaojuan Lu , Longwei Qiao , Yuting Liang , Qiping Zheng

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post-transcriptionally, often playing critical roles in various biological processes. Recent studies have highlighted the involvement of miRNAs in chondrogenesis by targeting key marker genes. Among these, miR-101a has been identified as a significant regulator, previously reported to target cyclooxygenase-2 (Cox-2, ptgs2) in various contexts. Here, we investigate the role of miR-101a in chondrocyte hypertrophy and osteoarthritis (OA) progression, focusing on its regulation of Col10a1 expression. Using multiple web-based tools (TargetScan, PicTar, miRDB, and miRCODE), we identified miR-101a as a potential regulator of Col10a1. Our in vitro experiments demonstrated that miR-101a was down-regulated during chondrocyte hypertrophy in MCT and ATDC5 cells, while Col10a1 and Cox-2 expression levels were up-regulated. Overexpression of miR-101a via mimics resulted in a significant decrease in Col10a1 and Cox-2 at both mRNA and protein levels, whereas inhibition of miR-101a led to their up-regulation. Additionally, MMP-13 protein levels were reduced upon miR-101a overexpression, with no significant changes in Sox9 and Runx2 expression. Luciferase reporter assays confirmed that Cox-2 was a direct target of miR-101a, suggesting that miR-101a indirectly regulates Col10a1 expression via Cox-2. In vivo, intra-articular injection of miR-101a mimics in a medial meniscus-induced OA mouse model resulted in decreased Col10a1 expression and reduced articular damage, supporting the protective role of miR-101a in OA progression. Our findings highlight miR-101a as a negative regulator of chondrocyte hypertrophy through Cox-2, and could be a potential target for further exploration in OA therapy.

MicroRNAs （miRNAs）是一种小的非编码rna，在转录后调节基因表达，通常在各种生物过程中发挥关键作用。最近的研究强调了mirna通过靶向关键标记基因参与软骨形成。其中，miR-101a已被确定为一个重要的调节因子，先前报道在各种情况下靶向环氧化酶-2 （Cox-2, ptgs2）。在这里，我们研究了miR-101a在软骨细胞肥大和骨关节炎（OA）进展中的作用，重点研究了其对Col10a1表达的调节。使用多种基于网络的工具（TargetScan、PicTar、miRDB和miRCODE），我们确定miR-101a是Col10a1的潜在调节因子。我们的体外实验表明，miR-101a在MCT和ATDC5细胞的软骨细胞肥大过程中下调，而Col10a1和Cox-2的表达水平上调。通过模拟物过表达miR-101a导致Col10a1和Cox-2 mRNA和蛋白水平显著降低，而抑制miR-101a导致其上调。此外，miR-101a过表达后，MMP-13蛋白水平降低，而Sox9和Runx2的表达无显著变化。荧光素酶报告基因检测证实Cox-2是miR-101a的直接靶点，提示miR-101a通过Cox-2间接调控Col10a1的表达。在体内，在内侧半月板诱导的OA小鼠模型中，关节内注射miR-101a模拟物导致Col10a1表达降低，关节损伤减轻，支持miR-101a在OA进展中的保护作用。我们的研究结果强调miR-101a通过Cox-2作为软骨细胞肥大的负调节因子，可能是OA治疗中进一步探索的潜在靶点。

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引用次数: 0

TNFAIP8/TIPE2 inactivation modulates extracellular matrix organization gene expression and preserves the intervertebral disc structure in mice TNFAIP8/TIPE2失活可调节细胞外基质组织基因的表达，保留小鼠椎间盘结构

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2025-08-30 DOI: 10.1016/j.gendis.2025.101835

Zuozhen Tian , Ken Chen , Frances S. Shofer , Srish S. Chenna , Daniel Z. Sandroni , Ling Qin , Yejia Zhang

引用次数: 0

Blockage of SUMO E1 enzyme inhibits ocular lens fibrosis by mediating SMAD4 SUMOylation SUMO E1酶阻断通过介导SMAD4 SUMO酰化抑制晶状体纤维化。

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2025-08-28 DOI: 10.1016/j.gendis.2025.101827

Min Hou , Yujie Ding , Xuan Bao , Liangping Liu , Yulan Wang , Mingxing Wu

The ocular lens serves as an exemplary biological model for investigating mechanisms of fibrotic disease, particularly through its well-characterized epithelial–mesenchymal transition (EMT) process. In lens capsular fibrosis, lens epithelial cells (LECs) undergo phenotypic transformation mediated by the dysregulation of a complex signaling network. While multiple interconnected pathways have been implicated in this pathogenic process, current therapeutic strategies for anterior subcapsular cataract and postoperative capsular opacification remain predominantly surgical, underscoring the urgent need for targeted pharmacological interventions. SUMOylation, an essential post-translational modification system, orchestrates critical cellular processes, including gene expression, genome integrity, and cell cycle progression. Emerging evidence positions SUMOylation as a critical regulator of EMT in both fibrotic disorders and oncogenesis. Building on these insights, we hypothesized that SUMO-mediated post-transitional modifications may drive LEC transdifferentiation in lens fibrotic pathologies. Our experimental findings demonstrated that elevated global SUMOylation (SUMO1/2/3 conjugates) in human anterior subcapsular cataract specimens correlated with fibrotic progression. Sole SUMO isoform deficiency partially mitigated TGFβ₂-driven EMT and injury-induced anterior subcapsular cataract. SUMO E1 overexpression enhanced LEC proliferative capacity, migration potential, and EMT progression. Pharmacological SUMO E1 inhibition (ML792) suppressed TGFβ₂-induced SMAD4 SUMOylation, nuclear translocation, a critical TGFβ/SMAD signaling event. ML792 also eliminated TGFβ₂-induced LEC EMT and experimental anterior subcapsular cataract. Our results establish SMAD4 SUMOylation as a pivotal molecular switch in lens fibrosis pathogenesis. Employing inhibitory drugs of SUMO conjugation in the years to come has the potential to be a novel therapeutic strategy for fibrotic cataracts.

晶状体是研究纤维化疾病机制的典型生物学模型，特别是通过其具有良好特征的上皮-间质转化（EMT）过程。在晶状体囊纤维化中，晶状体上皮细胞（LECs）经历由复杂信号网络失调介导的表型转化。虽然这一致病过程涉及多种相互关联的途径，但目前对前囊下白内障和术后囊混浊的治疗策略仍以手术为主，因此迫切需要有针对性的药物干预。SUMOylation是一个重要的翻译后修饰系统，它协调了关键的细胞过程，包括基因表达、基因组完整性和细胞周期进程。新出现的证据表明，sumo酰化在纤维化疾病和肿瘤发生中都是EMT的关键调节因子。基于这些见解，我们假设sumo介导的过渡后修饰可能驱动晶状体纤维化病理中的LEC转分化。我们的实验结果表明，人类前囊下白内障标本中sumo酰化（sumo /2/3共轭物）的升高与纤维化进展相关。脚底SUMO异构体缺乏部分减轻tgf β2驱动的EMT和损伤性前囊下白内障。SUMO E1过表达增强LEC增殖能力、迁移潜力和EMT进展。药理SUMO E1抑制（ML792）抑制TGFβ2诱导的SMAD4 SUMOylation，核易位，一个关键的TGFβ/SMAD信号事件。ML792还能消除tgf β2诱导的LEC EMT和实验性前囊下白内障。我们的研究结果证实SMAD4 SUMOylation是晶状体纤维化发病机制中的关键分子开关。在未来的几年里，使用抑制SUMO结合的药物有可能成为纤维化白内障的一种新的治疗策略。

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引用次数: 0

Overview of glutamine metabolism in stromal components of the tumor microenvironment and potential anti-tumor therapies 肿瘤微环境基质成分谷氨酰胺代谢及潜在抗肿瘤治疗综述

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2025-08-26 DOI: 10.1016/j.gendis.2025.101834

Zizhuo Li , Jiapeng Deng , Hai Wang , Tao Liu , Yuyang Zhou , Pei Ouyang , Xuan Liang , Xian Zhang , Songtao Qi , Yaomin Li

As a critical metabolite in the tumor microenvironment, glutamine plays a crucial role in tumor progression, and its dual effects on promoting and inhibiting tumors have garnered increasing attention in recent years. Glutamine metabolism in tumor cells has been extensively studied; however, there is currently a lack of a comprehensive description of how it interacts with tumor stromal components in the tumor microenvironment. This review focuses on the interaction of glutamine metabolism and a range of tumor stromal components, such as macrophages, dendritic cells, T cells, fibroblasts, collagen, and blood vessels in the tumor microenvironment, as well as a summary of current prospective anti-tumor therapeutics targeting glutamine metabolism. Furthermore, this study discusses the shortcomings of mechanism research, metabolic complexity, and metabolic therapy for glutamine metabolism and proposes future research directions that are expected to provide a theoretical foundation for clinical cancer treatment strategies.

谷氨酰胺作为肿瘤微环境中的关键代谢物，在肿瘤的进展中起着至关重要的作用，其促进和抑制肿瘤的双重作用近年来越来越受到人们的关注。谷氨酰胺在肿瘤细胞中的代谢已被广泛研究；然而，目前缺乏对其在肿瘤微环境中如何与肿瘤基质成分相互作用的全面描述。本文综述了谷氨酰胺代谢与肿瘤微环境中一系列肿瘤基质成分（如巨噬细胞、树突状细胞、T细胞、成纤维细胞、胶原蛋白和血管）的相互作用，并综述了目前针对谷氨酰胺代谢的前瞻性抗肿瘤治疗方法。此外，本研究还讨论了谷氨酰胺代谢机制研究、代谢复杂性、代谢治疗等方面存在的不足，并提出了未来的研究方向，以期为临床肿瘤治疗策略提供理论依据。

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引用次数: 0

DNA methylation heterogeneity in complex tumor microenvironment: Quantitative methods, influencing factors, and clinical implications 复杂肿瘤微环境中的DNA甲基化异质性：定量方法、影响因素和临床意义

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2025-08-25 DOI: 10.1016/j.gendis.2025.101832

Yongle Xu , Shuangyue Ma , Manyi Xu , Hongbo Zhu , Yuncong Wang , Wenbo Dong , Jing Gan , Yusen Zhao , Xinrong Li , Shuangshuang Wang , Haoyu Hu , Jiaheng He , Shangwei Ning , Hui Zhi

5-Methylcytosine (5-mC) is the most prevalent DNA methylation modification in the human genome, and its abnormal patterns are strongly associated with tumor progression. Intratumoral and intertumoral DNA methylation heterogeneity (DNAmeH) primarily arises from cancer epigenome heterogeneity and the diverse cell compositions within the tumor microenvironment (TME). Furthermore, recent advancements in high-throughput sequencing and microarray technologies have facilitated the development of quantitative methods for measuring DNAmeH, enabling a more thorough exploration of the factors influencing it. Moreover, investigating various DNA methylation patterns at the single-cell level within the intricate TME sheds light on DNAmeH being driven by cellular heterogeneity. In addition, accumulating studies on the selection of methylation biomarkers in tissue or circulating DNA elucidate the cell specificity of DNA methylation, which is valuable for early cancer detection and personalized therapy. In this review, we elucidate the characteristics of intratumoral and intertumoral DNAmeH, considering DNAmeH differences across cancer types, among individual cells, and at allele-specific hemimethylation sites. Several metrics are summarized to quantitatively assess DNAmeH. We evaluate the factors that influence DNAmeH via these metrics, including the cell cycle phase, tumor mutational burden (TMB), cellular stemness, copy number variation (CNV), tumor subtype, tumor characteristics, tumor stage, state of tumor cells, hypoxia, and tumor purity. Finally, we highlight the deconvolution of TME cellular components and the application of predictive methylation biomarkers in cancer clinical research.

5-甲基胞嘧啶（5-mC）是人类基因组中最常见的DNA甲基化修饰，其异常模式与肿瘤进展密切相关。肿瘤内和肿瘤间DNA甲基化异质性（DNAmeH）主要源于肿瘤表观基因组异质性和肿瘤微环境（TME）内不同的细胞组成。此外，高通量测序和微阵列技术的最新进展促进了测量DNAmeH的定量方法的发展，使人们能够更彻底地探索影响它的因素。此外，在复杂的TME中，在单细胞水平上研究各种DNA甲基化模式揭示了细胞异质性驱动的DNAmeH。此外，组织或循环DNA中甲基化生物标志物的选择研究不断积累，阐明了DNA甲基化的细胞特异性，这对癌症的早期检测和个性化治疗具有重要价值。在这篇综述中，我们阐述了肿瘤内和肿瘤间DNAmeH的特征，考虑了不同癌症类型、个体细胞和等位基因特异性半甲基化位点的DNAmeH差异。总结了几个指标来定量评估DNAmeH。我们通过这些指标评估影响DNAmeH的因素，包括细胞周期期、肿瘤突变负荷（TMB）、细胞干性、拷贝数变异（CNV）、肿瘤亚型、肿瘤特征、肿瘤分期、肿瘤细胞状态、缺氧和肿瘤纯度。最后，我们强调了TME细胞成分的反卷积和预测甲基化生物标志物在癌症临床研究中的应用。

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引用次数: 0