Cancer Genetics最新文献

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M6A methylation in thyroid cancer: Functions, mechanisms, and clinical significance 甲状腺癌中M6A甲基化：功能、机制和临床意义

IF 2.1 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2026-01-10 DOI: 10.1016/j.cancergen.2026.01.005

Dongye Huang , Zhuoya Xie , Senmin Zhang , Yaorong Su , Chang Liu , Wenkuan Chen

Thyroid cancer (TC), the most prevalent endocrine malignancy, exhibits marked biological heterogeneity and a persistent therapeutic gap in aggressive, treatment-refractory subsets. N6-methyladenosine (m6A), pervasive across eukaryotic RNA processing—splicing, maturation, stability, translation, and localization—constitutes a central layer of epigenetic regulation. By reshaping post-transcriptional programs, m6A modifications govern tumor initiation and progression, sustaining stemness, accelerating proliferation and invasion, and mediating therapy resistance. A growing body of evidence implicates dysregulated m6A regulators in TC pathogenesis; yet the multiplicity of effectors and their context-dependent actions complicate mechanistic resolution. This review synthesizes current advances, delineating m6A’s involvement in four cardinal arenas of thyroid tumorigenesis: altered cellular behaviors (proliferation, migration), metabolic reprogramming, programmed cell death (apoptosis and ferroptosis), and resistance to targeted, radioactive iodine, and immunotherapeutic strategies. We further examine the emerging interface between m6A and non-coding RNAs, highlighting how this axis rewires oncogenic networks. Finally, we appraise the translational potential of m6A as a diagnostic and prognostic biomarker and as a therapeutic target, offering perspective on opportunities and challenges for epitranscriptome-guided precision oncology in TC.

甲状腺癌（TC）是最常见的内分泌恶性肿瘤，在侵袭性、难治性亚群中表现出明显的生物学异质性和持续的治疗差距。n6 -甲基腺苷（m6A）普遍存在于真核RNA加工过程中——剪接、成熟、稳定、翻译和定位——构成了表观遗传调控的核心层。通过重塑转录后程序，m6A修饰控制肿瘤的发生和发展，维持干细胞，加速增殖和侵袭，并介导治疗抵抗。越来越多的证据表明m6A调节因子失调与TC发病有关；然而，效应器的多样性及其依赖于环境的作用使机制解决复杂化。这篇综述综合了目前的进展，描述了m6A参与甲状腺肿瘤发生的四个主要领域：细胞行为改变（增殖、迁移）、代谢重编程、程序性细胞死亡（凋亡和铁死亡）、对靶向、放射性碘和免疫治疗策略的抗性。我们进一步研究了m6A和非编码rna之间的新界面，强调了该轴如何重新连接致癌网络。最后，我们评估了m6A作为诊断和预后生物标志物以及治疗靶点的转化潜力，为TC中表转录组引导的精确肿瘤学提供了机遇和挑战的视角。

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引用次数: 0

Investigation of hnRNPK's role in gastric cancer proliferation and migration and its interaction with TL1A hnRNPK在胃癌增殖和迁移中的作用及其与TL1A相互作用的研究

IF 2.1 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2026-01-06 DOI: 10.1016/j.cancergen.2026.01.004

Sihan Bo , Tao Jiang , Yong You , Shuang Tian , Bing Bai , Yu Cheng , Yaxian Gao , Yongwei Wang

The present investigation elucidated the pivotal involvement of heterogeneous nuclear ribonucleoprotein K (hnRNPK) in the oncogenic advancement of gastric carcinoma through an integrative, multi-tiered analytical framework. Quantitative tissue microarray assessments indicated that elevated hnRNPK abundance exhibited a marked association with tumor differentiation grade, lymphatic dissemination, TNM classification, and unfavorable clinical outcome. Mechanistic exploration further substantiated that hnRNPK, predominantly confined to the nuclear compartment, facilitates gastric tumor aggressiveness by modulating the PI3K/Akt transduction cascade. Both in vivo and in vitro assays consistently verified that hnRNPK markedly augments the proliferative and motile potentials of gastric carcinoma cells. Importantly, this research constitutes the initial report delineating a molecular linkage between hnRNPK activity and gastric cancer pathogenesis. Rescue experiments demonstrated that TL1A knockdown in hnRNPK-overexpressing cells significantly reversed pro-tumor phenotypes, suggesting that hnRNPK exerts its oncogenic effects at least partially through a TL1A-dependent mechanism. These findings not only provide insights into the molecular mechanism of hnRNPK in GC but also offer experimental evidence for developing novel therapeutic strategies targeting the hnRNPK-TL1A axis in GC.

本研究通过一个综合的、多层次的分析框架阐明了异质性核核糖核蛋白K （hnRNPK）在胃癌发生进展中的关键作用。定量组织微阵列评估显示，hnRNPK丰度升高与肿瘤分化等级、淋巴播散、TNM分类和不良临床结果显著相关。机制探索进一步证实，主要局限于核室的hnRNPK通过调节PI3K/Akt转导级联促进胃肿瘤的侵袭性。体内和体外实验一致证实，hnRNPK显著增强胃癌细胞的增殖和运动潜能。重要的是，这项研究首次报道了hnRNPK活性与胃癌发病机制之间的分子联系。救援实验表明，TL1A敲低在hnRNPK过表达的细胞中显著逆转了促瘤表型，这表明hnRNPK至少部分通过TL1A依赖机制发挥其致癌作用。这些发现不仅为hnRNPK在GC中的分子机制提供了新的见解，也为开发针对GC中hnRNPK- tl1a轴的新治疗策略提供了实验证据。

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引用次数: 0

Identifying transcriptional signatures of leukocytes in tissue and blood for multicancer diagnosis by using machine learning methods 利用机器学习方法识别组织和血液中白细胞的转录特征，用于多癌诊断

IF 2.1 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2026-01-05 DOI: 10.1016/j.cancergen.2026.01.003

QingLan Ma , JingXin Ren , Lei Chen , Wei Guo , KaiYan Feng , Yu Zhang , WenFeng Shen , Tao Huang , Yu-Dong Cai

Investigating the transcriptional signatures of immune cells in various cancer types is crucial for understanding their roles in the tumor microenvironment and developing effective immunotherapeutic strategies. In this study, we employed machine learning methods to analyze RNA-seq data from patients with four different types of cancers and two immune cell types, including T cell and CD45+CD3− leukocyte cell types. We processed seven datasets, each divided into three groups on the basis of cell source: tumor, normal adjacent tissue, and peripheral blood. The datasets were downscaled by using the Boruta method, and the remaining genes were ranked for criticality in a list through the max-relevance and min-redundancy method. The obtained list of genes was fed into incremental feature selection (IFS), which employed decision tree or random forest to distinguish cells, for the identification of key genes associated with immune cell function in different cancer types and construction of efficient classifiers and classification rules (special patterns for different groups). Our results revealed distinct expression patterns of key genes, such as the downregulation of CST7 in T cells from tumor tissues and differential expression of CD2 in non-tumor sites. Furthermore, we identified LCP1, CD27, and MAL as immunologically relevant genes in T cells across different tissue origins, whereas IFI30, CXCR4, and FOSB played various roles in CD45+CD3− leukocytes. The identified key genes were supported by evidence in the literature, highlighting their involvement in antitumor processes in T cells and other immune cells. Our findings provide valuable insights into the transcriptional signatures of immune cells in different cancer types and lay the foundation for the development of novel diagnostic, prognostic, and therapeutic strategies in cancer immunology.

研究不同类型癌症中免疫细胞的转录特征对于理解它们在肿瘤微环境中的作用和制定有效的免疫治疗策略至关重要。在这项研究中，我们采用机器学习方法分析了四种不同类型癌症患者和两种免疫细胞类型（包括T细胞和CD45+CD3−白细胞类型）的RNA-seq数据。我们处理了七个数据集，每个数据集根据细胞来源分为三组：肿瘤、正常邻近组织和外周血。采用Boruta方法对数据集进行缩减，并通过最大相关性和最小冗余度方法对剩余基因进行关键度排序。将获得的基因列表输入到采用决策树或随机森林进行细胞区分的增量特征选择（IFS）中，鉴定不同癌症类型中与免疫细胞功能相关的关键基因，并构建有效的分类器和分类规则（不同群体的特殊模式）。我们的研究结果揭示了关键基因的不同表达模式，如肿瘤组织T细胞中CST7的下调和非肿瘤部位CD2的差异表达。此外，我们发现LCP1、CD27和MAL在不同组织来源的T细胞中是免疫相关基因，而IFI30、CXCR4和FOSB在CD45+CD3−白细胞中发挥着不同的作用。鉴定出的关键基因得到了文献证据的支持，强调了它们参与T细胞和其他免疫细胞的抗肿瘤过程。我们的发现为了解不同癌症类型中免疫细胞的转录特征提供了有价值的见解，并为癌症免疫学中新的诊断、预后和治疗策略的发展奠定了基础。

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引用次数: 0

In silico identification of deleterious NT5C2 and PRPS1 mutations driving thiopurine resistance in relapsed acute lymphoblastic leukemia 恶性nt52c和PRPS1突变驱动复发性急性淋巴细胞白血病硫嘌呤耐药的计算机鉴定

IF 2.1 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2026-01-04 DOI: 10.1016/j.cancergen.2026.01.001

Ramita Sharma , Jeeshitha Kudithipudi , Himanshu Singh , Dhamodharan Prabhu , Sugunakar Vuree

Relapse in Acute Lymphoblastic Leukemia (ALL) are often driven by multiple factors, including thiopurine drug-resistant mutations in NT5C2 and PRPS1. To determine the functional significance of these mutations, we employed comprehensive computational methods to assess their impact on protein stability, evolutionary conservation, and possible drug sensitivity, as well as molecular docking and simulations with 6-MP and 6-TG to show the impact of these mutations on drug binding. The top-ranked pathogenic variants investigated, NT5C2 rs775844720 (D431V) and PRPS1 rs2147684832 (D224G), exhibited the most pronounced destabilizing effects on proteins. Protein-protein interaction networks indicate that these variations are involved in nucleotide metabolism and pharmacological responses, confirming their role in thiopurine resistance. In summary, NT5C2 and PRPS1 gene variations may act as potential biomarkers for resistance and hence require more experimental validation of VUS to determine their significance.

急性淋巴细胞白血病（ALL）的复发通常由多种因素驱动，包括NT5C2和PRPS1中硫嘌呤耐药突变。为了确定这些突变的功能意义，我们采用综合计算方法评估它们对蛋白质稳定性、进化保守性和可能的药物敏感性的影响，并与6-MP和6-TG进行分子对接和模拟，以显示这些突变对药物结合的影响。排名前几位的致病变异NT5C2 rs775844720 （D431V）和PRPS1 rs2147684832 （D224G）对蛋白质表现出最明显的不稳定作用。蛋白质-蛋白质相互作用网络表明，这些变异参与核苷酸代谢和药理反应，证实了它们在硫嘌呤耐药中的作用。总之，NT5C2和PRPS1基因变异可能作为潜在的耐药生物标志物，因此需要更多的VUS实验验证来确定其意义。

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引用次数: 0

Plasma cell-free DNA biomarkers as novel diagnostic and prognostic tools in breast cancer 血浆无细胞DNA生物标志物作为乳腺癌诊断和预后的新工具

IF 2.1 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-12-24 DOI: 10.1016/j.cancergen.2025.12.004

Rofida M. Abd El-Fatah , Heba K. Badawy , Heba F. Pasha , Noha M. Mesbah , Dina M. Abo-Elmatty , Asmaa R. Abdel-Hamed

Breast cancer remains the leading cause of cancer-related deaths among women, underscoring the need for more sensitive and specific biomarkers. Traditional markers such as CA15-3 lack sufficient diagnostic and prognostic accuracy. Quantification of plasma cell-free DNA (cfDNA) offers a minimally invasive liquid-biopsy approach for tumor detection and monitoring. This case–control study assessed a cfDNA panel comprising KLK10, SOX17, WNT5A, and MSH2 in 100 breast cancer patients and 100 matched controls. Plasma cfDNA levels, quantified by qPCR, and CA15-3 levels, measured by ELISA, were evaluated for diagnostic and prognostic value using ROC analyses and a 35-month follow-up for survival endpoints. All cfDNA genes were significantly elevated in patients (p<0.001) and exhibited superior diagnostic accuracy versus CA15-3, with MSH2 showing the highest AUC (95.3%), sensitivity (92%), and specificity (89%). Elevated cfDNA correlated strongly with metastasis and adverse pathological features, outperforming CA15-3 in predicting metastasis (AUC = 0.962–0.987). High cfDNA concentrations associated with poorer disease-free and overall survival (p<0.001). Detection of a cfDNA panel, rather than a single gene, demonstrates superior utility as a minimally invasive biomarker promising for early detection, risk assessment, and disease monitoring in breast cancer.

乳腺癌仍然是女性癌症相关死亡的主要原因，这凸显了对更敏感、更特异的生物标志物的需求。传统的标志物如CA15-3缺乏足够的诊断和预后准确性。血浆游离DNA （cfDNA）的定量为肿瘤检测和监测提供了一种微创液体活检方法。本病例对照研究评估了包括KLK10、SOX17、WNT5A和MSH2在内的cfDNA面板，涉及100名乳腺癌患者和100名匹配对照。采用qPCR定量的血浆cfDNA水平和ELISA测定的CA15-3水平，通过ROC分析和35个月的生存终点随访来评估诊断和预后价值。所有cfDNA基因在患者中均显著升高（p<0.001），并且与CA15-3相比具有更高的诊断准确性，其中MSH2显示出最高的AUC(95.3%)，灵敏度（92%）和特异性（89%）。cfDNA升高与转移及不良病理特征密切相关，在预测转移方面优于CA15-3 （AUC = 0.962 ~ 0.987）。高cfDNA浓度与较差的无病生存和总生存相关（p<0.001）。检测cfDNA组，而不是单个基因，作为一种微创生物标志物，有望在乳腺癌的早期检测、风险评估和疾病监测中发挥更大的作用。

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引用次数: 0

Single-Step CRISPR/Cas13a Assay for detection of small RNAs in Saliva : a proof-of-concept study 单步CRISPR/Cas13a检测唾液中小rna：一项概念验证研究

IF 2.1 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-12-12 DOI: 10.1016/j.cancergen.2025.12.003

Devyani Salodkar , Sheetal Dongarwar , Aparna Nair , Prajkta Ashtaputre , Shreya Reddy , Shrutam Somkuwar , Deovrat Begde

Objective

We describe a proof-of-concept study of a rapid, single-step CRISPR/Cas13a assay using Leptotrichia wadei (LwCas13a) for the detection of small RNA (miRNA) biomarkers in saliva, and compare its performance to real-time PCR (RT-PCR).

Methods

The single-step Cas13a assay was evaluated against RT-PCR for its detection efficiency, sensitivity, specificity, and its ability to function in a complex biological matrix. A proof-of-concept test was conducted on patient saliva samples to detect a known oral cancer biomarker, hsa-miR-21–3p

Results

The Cas13a assay successfully detected candidate miRNA at picomolar concentrations in both in vitro and saliva samples, demonstrating sensitivity and specificity comparable to RT-PCR. Notably, the assay provided discernible detection of the cancer biomarker directly in patient saliva without the need for RNA extraction or reverse transcription steps.

Conclusion

The proposed single-step CRISPR/Cas13a assay may be developed into a promising platform for developing quick and affordable point-of-care diagnostics for cancer and other diseases, circumventing the need for expensive and time-consuming sample preparation steps.

目的：我们描述了一项使用wdei细毛菌（Leptotrichia wadei, LwCas13a）快速单步CRISPR/Cas13a检测唾液中小RNA （miRNA）生物标志物的概念验证研究，并将其性能与实时PCR （RT-PCR）进行比较。方法将单步Cas13a检测方法与RT-PCR相比较，比较其检测效率、灵敏度、特异性以及在复杂生物基质中的功能。在患者唾液样本中进行了概念验证测试，以检测已知的口腔癌生物标志物hsa- mir -21 - 3prepresultcas13a试验成功地在体外和唾液样本中检测到皮摩尔浓度的候选miRNA，显示出与RT-PCR相当的敏感性和特异性。值得注意的是，该分析提供了直接在患者唾液中可识别的癌症生物标志物检测，而无需RNA提取或逆转录步骤。结论提出的单步CRISPR/Cas13a检测方法有望发展成为一个有前景的平台，用于开发快速且价格合理的癌症和其他疾病的即时诊断，避免了昂贵且耗时的样品制备步骤。

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引用次数: 0

Exploration of a prognostic model for childhood acute lymphoblastic leukemia 儿童急性淋巴细胞白血病预后模型的探讨。

IF 2.1 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-12-09 DOI: 10.1016/j.cancergen.2025.12.002

Yu Bai , Wen-wen Feng , Lan Tang , Yan-qing Sun

引用次数: 0

Genetic modulation of ABCB1: Sunvozertinib reverses ABCB1-mediated multidrug resistance in cancer cells ABCB1的遗传调控：Sunvozertinib逆转ABCB1介导的癌症细胞多药耐药。

IF 2.1 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-12-02 DOI: 10.1016/j.cancergen.2025.12.001

Lu-Qi Cao , Yuhao Xie , Xuanyu Chen , Harsh Patel , Luoxi Yuan , John Wurpel , Kunxiang Gong , Zhe-Sheng Chen

Sunvozertinib is an oral, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) designed to treat non-small cell lung cancer (NSCLC) patients with EGFR exon 20 insertion mutations under a phase II clinical trial. In this study, we investigated whether sunvozertinib could antagonize ABCB1, also known as multidrug resistance 1 (MDR1/P-gp). ABCB1 is a gene that encodes an important drug transport protein that pumps various substances, including drugs and toxins, out of cells. Sunvozertinib received a high score in docking analysis, indicating a strong interaction between sunvozertinib and ABCB1. ATPase assay indicated that sunvozertinib stimulated ABCB1 ATPase activity in a concentration-dependent manner. MTT assay shows that sunvozertinib significantly reversed ABCB1-mediated MDR but not ABCC1- and ABCG2-mediated MDR. Mechanistic studies show that sunvozertinib significantly reversed ABCB1-mediated MDR by attenuating the efflux activity of the ABCB1 transporter. Furthermore, treatment with sunvozertinib did not change protein expression or subcellular localization of ABCB1. Altogether, these data demonstrate that sunvozertinib, when combined with other conventional chemotherapeutic agents, can overcome MDR and improve therapeutic effect.

Sunvozertinib是一种口服、不可逆的表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI），正在进行II期临床试验，旨在治疗EGFR外显子20插入突变的非小细胞肺癌（NSCLC）患者。在这项研究中，我们研究了sunvozertinib是否可以拮抗ABCB1，也被称为多药耐药1 （MDR1/P-gp）。ABCB1是一种编码一种重要药物转运蛋白的基因，该蛋白将包括药物和毒素在内的各种物质泵出细胞。在对接分析中，Sunvozertinib获得高分，说明Sunvozertinib与ABCB1之间存在较强的相互作用。atp酶测定表明，sunvozertinib以浓度依赖性的方式刺激ABCB1 atp酶活性。MTT试验显示，sunvozertinib显著逆转abcb1介导的MDR，但对ABCC1-和abcg2介导的MDR无显著逆转作用。机制研究表明，sunvozertinib通过减弱ABCB1转运体的外排活性显著逆转ABCB1介导的MDR。此外，sunvozertinib治疗不会改变ABCB1的蛋白表达或亚细胞定位。综上所述，这些数据表明，当与其他常规化疗药物联合使用时，sunvozertinib可以克服MDR，提高治疗效果。

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引用次数: 0

Multiple endocrine neoplasia type 1 syndrome due to novel Alu insertion 新型Alu插入引起的多发性内分泌肿瘤1型综合征

IF 2.1 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-12-01 DOI: 10.1016/j.cancergen.2025.11.014

Aislinn Cragg , Hannah Boon , Treena Cranston , Tristan Richardson , Schaida Schirwani

Multiple Endocrine Neoplasia type 1 syndrome is caused by pathogenic variants in the MEN1 gene, and is characterised by tumours in multiple endocrine glands. This case study looks at a family with four affected members over two generations who have been diagnosed with the syndrome after next generation sequencing identified a novel Alu insertion. Previous genetic testing in the index patient had not identified an underlying cause.

多发性内分泌肿瘤1型综合征是由MEN1基因的致病性变异引起的，其特征是多个内分泌腺体的肿瘤。本案例研究观察了一个有四名受影响成员的家庭，他们在下一代测序发现了一个新的Alu插入后被诊断为该综合征。先前对该患者的基因检测未发现潜在病因。

引用次数: 0

Corrigendum to “Study on the Anticancer Mechanism of Hydroxygenkwanin in Esophageal Cancer via the ESRRA Signaling Pathway” [Cancer Genetics, 298–299, (2025) Pages 180-192] “羟基根wanin在食管癌中ESRRA信号通路的抗癌机制研究”的勘误表[Cancer Genetics， 298-299, (2025) page 180-192]。

IF 2.1 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-11-29 DOI: 10.1016/j.cancergen.2025.11.009

Yuan Wang , Li XinWan , Yutian Zhang , Qi Jia , Chao Li , Xiaonan Cui

引用次数: 0

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