Cancer Genetics最新文献

Genetic polymorphisms of tumor necrosis factor receptor-associated factor 3 and their association with acute lymphoblastic leukemia 肿瘤坏死因子受体相关因子3的遗传多态性及其与急性淋巴细胞白血病的关系

IF 2.1 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2026-01-27 DOI: 10.1016/j.cancergen.2026.01.012

Fadwa M Alkhulaifi , Hana Hakami , Jamilah Alshammari , Safa A Alqarzae , Aeshah Almuhaini , Sheka Y Aloyouni , Suliman Alomar

Background

Acute lymphoblastic leukemia (ALL) is an aggressive hematological malignancy driven by genetic and immunological dysregulation. Tumor necrosis factor receptor-associated factor 3 (TRAF3) plays an essential role in regulating immune signaling, lymphocyte homeostasis, and NF-κB pathways. Although TRAF3 alterations have been implicated in various immune disorders and hematologic cancers, the contribution of TRAF3 genetic polymorphisms to ALL susceptibility remains insufficiently understood.

Purpose

To investigate the association between three TRAF3 single nucleotide polymorphisms (SNPs); rs33980500, rs13210247, and rs1131877, and ALL susceptibility in Saudi patients, and to evaluate TRAF3 mRNA expression levels in ALL compared to healthy individuals.

Methods

A case-control study was conducted involving 150 newly diagnosed ALL patients and 115 age- and sex-matched healthy controls. Genotyping of the selected TRAF3 SNPs was performed using TaqMan allelic discrimination assays. TRAF3 mRNA expression in peripheral blood white cells was quantified through RT-qPCR. Statistical analyses included genotype/allele frequency comparisons, odds ratios, Hardy-Weinberg equilibrium testing, linkage disequilibrium assessment, and haplotype construction.

Results

None of the analyzed SNPs showed a statistically significant association with ALL across genotype, allele, or haplotype models. Linkage disequilibrium between the SNPs was absent. However, TRAF3 mRNA expression was significantly upregulated in ALL patients, exhibiting a 3.88-fold increase compared with controls (p < 0.05).

Conclusion

Although the examined TRAF3 SNPs were not associated with ALL susceptibility in this cohort, the marked elevation of TRAF3 mRNA expression suggests a potential role for TRAF3-related signaling in ALL pathogenesis. TRAF3 expression may represent a promising biomarker warranting further investigation.

急性淋巴细胞白血病（ALL）是一种由遗传和免疫失调驱动的侵袭性血液系统恶性肿瘤。肿瘤坏死因子受体相关因子3 （Tumor necrosis factor receptor-associated factor 3, TRAF3）在调节免疫信号、淋巴细胞稳态和NF-κB通路中发挥重要作用。尽管TRAF3的改变与各种免疫疾病和血液学癌症有关，但TRAF3基因多态性对ALL易感性的影响仍未得到充分的了解。目的探讨TRAF3单核苷酸多态性（snp）的相关性；rs33980500、rs13210247和rs1131877与沙特患者ALL易感性的关系，并与健康个体比较ALL中TRAF3 mRNA的表达水平。方法采用病例对照研究，纳入150例ALL新诊断患者和115例年龄、性别匹配的健康对照。采用TaqMan等位基因鉴别法对所选TRAF3 snp进行基因分型。RT-qPCR检测外周血白细胞中TRAF3 mRNA的表达。统计分析包括基因型/等位基因频率比较、优势比、Hardy-Weinberg平衡检验、连锁不平衡评估和单倍型构建。结果分析的snp中没有一个与ALL在基因型、等位基因或单倍型模型中具有统计学意义的相关性。snp之间不存在连锁不平衡。然而，TRAF3 mRNA的表达在ALL患者中显著上调，与对照组相比增加了3.88倍（p < 0.05）。结论虽然在该队列中检测的TRAF3 snp与ALL易感性无关，但TRAF3 mRNA表达的显著升高提示TRAF3相关信号在ALL发病机制中可能起作用。TRAF3的表达可能是一种有希望的生物标志物，值得进一步研究。

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引用次数: 0

Germline APC I1307K and MITF E318K variants in a patient with high-grade serous ovarian carcinoma: A case report 高级别浆液性卵巢癌患者的种系APC I1307K和MITF E318K变异：一例报告

IF 2.1 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2026-01-24 DOI: 10.1016/j.cancergen.2026.01.011

Samantha C. Covey , Michelle M. De Jesus Ortiz , Amelia Jernigan , Ridin Balakrishnan , Sun Young Kim , Lucio Miele

We report the case of a 76‑year‑old woman with high‑grade serous ovarian carcinoma (HGSOC) who was found to carry germline variants in APC I1307K and MITF E318K. Although neither variant is an established contributor to ovarian cancer risk, their co‑occurrence raises the possibility of polygenic or modifier effects on tumor susceptibility. The APC I1307K allele is a founder variant linked to increased colorectal cancer risk through the creation of a hypermutable region that predisposes to somatic mutations rather than classical tumor‑suppressor inactivation. In contrast, MITF E318K is a gain‑of‑function variant associated with melanoma and renal cell carcinoma, acting through altered transcriptional regulation that promotes cell proliferation and survival. While these genes do not interact directly, both converge on signaling pathways—WNT/β‑catenin, MAPK/ERK, and PI3K/AKT—that are widely implicated in ovarian carcinogenesis. There is a possibility that HGSOC in this patient is sporadic and unrelated to these two variants. Nevertheless, the case underscores the importance of comprehensive germline testing and highlights potential, yet underexplored, genetic interactions that may influence ovarian cancer risk. To our knowledge, this represents the first reported case of HGSOC in a patient harboring both variants, offering a hypothesis‑generating observation for future investigation.

我们报告一例76岁女性高级别浆液性卵巢癌（HGSOC），发现携带APC I1307K和MITF E318K种系变异。虽然这两种变异都不是卵巢癌风险的确定因素，但它们的共同出现增加了多基因或修饰因子对肿瘤易感性影响的可能性。APC I1307K等位基因是一种创始变异，通过创建一个易发生体细胞突变而非经典肿瘤抑制因子失活的超可变区域，与结直肠癌风险增加有关。相反，MITF E318K是一种与黑色素瘤和肾细胞癌相关的功能增益变异，通过改变转录调节促进细胞增殖和存活。虽然这些基因不直接相互作用，但它们都聚集在信号通路上- wnt /β -连环蛋白，MAPK/ERK和PI3K/ akt -广泛参与卵巢癌的发生。该患者的HGSOC可能是散发性的，与这两种变异无关。尽管如此，该病例强调了全面生殖系检测的重要性，并强调了可能影响卵巢癌风险的潜在的、尚未充分探索的基因相互作用。据我们所知，这是首例同时携带两种变异的HGSOC病例，为未来的研究提供了假设。

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引用次数: 0

Persistent monosomy 7 in Philadelphia chromosome-negative cells without disease progression over nearly two decades of follow-up in chronic myeloid leukemia 在近20年的慢性髓性白血病随访中，费城染色体阴性细胞中无疾病进展的持续性单体7

IF 2.1 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2026-01-19 DOI: 10.1016/j.cancergen.2026.01.010

Menghao Chen , Guilin Tang , Shimin Hu

Monosomy 7 (−7) is frequently associated with myelodysplastic neoplasm/syndrome (MDS) and acute myeloid leukemia (AML). In chronic myeloid leukemia (CML), the acquisition of −7 in Philadelphia chromosome–positive (Ph-positive) cells is considered a high-risk feature for progression to blast crisis. However, the clinical significance of −7 in Ph-negative cells remains less unclear. We report a patient with CML who developed a − 7 clone in Ph-negative cells during tyrosine kinase inhibitor (TKI) therapy. The −7 clone emerged after 14 months of TKI treatment, persisted for nearly six years, and subsequently disappeared. The patient continued treatment with sequential TKIs under long-term surveillance. Over nearly 20 years of follow-up, there was no evidence of significant dysplasia or progression to AML. This case suggests that the occurrence of −7 in Ph-negative cells does not reflect TKI-induced genotoxicity and does not necessarily confer an increased risk of MDS or AML.

7号单体（−7）常与骨髓增生异常肿瘤/综合征（MDS）和急性髓性白血病（AML）相关。在慢性髓性白血病（CML）中，费城染色体阳性（ph阳性）细胞中−7的获得被认为是进展为细胞危象的高风险特征。然而，−7在ph阴性细胞中的临床意义尚不清楚。我们报告了一例CML患者在酪氨酸激酶抑制剂（TKI）治疗期间在ph阴性细胞中产生−7克隆。−7克隆在TKI治疗14个月后出现，持续了近6年，随后消失。患者在长期监测下继续接受序贯tki治疗。在近20年的随访中，没有明显的异常增生或AML进展的证据。该病例提示- 7在ph阴性细胞中的出现并不反映tki诱导的遗传毒性，也不一定会增加MDS或AML的风险。

引用次数: 0

Transcription factor FOXP2 attenuates the stemness of breast cancer cells by abolishing the transcription of Twist1. 转录因子FOXP2通过消除Twist1的转录来减弱乳腺癌细胞的干性。

IF 2.1 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2026-01-19 DOI: 10.1016/j.cancergen.2026.01.009

Taolin Chen, Yuxiang Liu, Li Yu, Yan Chen, Mingmin Huang, Yongjun Tan

Transcription factor FOXP2 participates in language acquisition and increasing evidence suggests that dysregulation of FOXP2 is associated with human tumorigenesis and progression. Reducing FOXP2 levels has increased breast cancer stem cell viability, but its inhibitory mechanisms to cancer stem cells are still not fully understood. In this study, we found that the expression levels of FOXP2 were downregulated in clinical breast cancers and negatively correlated with the cancer stem cell marker ALDH1. We demonstrated that the expression of FOXP2 was significantly decreased in the mammosphere formed by breast cancer cells. The overexpression of FOXP2 reduced the expression of cancer stem cell markers and consequently the mammosphere formation ability in breast cancer cells. We found that FOXP2 directly inhibited the transcription of Twist1, a proto-oncogene promoting the metastasis and stemness of cancer cells. The compensatory expression of Twist1 in FOXP2-overexpressing breast cancer cells counteracted FOXP2's inhibitory effects on the stemness of breast cancer cells. Together, the results showed that FOXP2 attenuated the stemness of breast cancer cells by abolishing the transcription of Twist1.

转录因子FOXP2参与语言习得，越来越多的证据表明FOXP2的失调与人类肿瘤的发生和发展有关。降低FOXP2水平可以提高乳腺癌干细胞的活力，但其对癌症干细胞的抑制机制尚不完全清楚。在本研究中，我们发现FOXP2在临床乳腺癌中表达水平下调，且与癌症干细胞标志物ALDH1呈负相关。我们发现FOXP2的表达在乳腺癌细胞形成的乳腺球中显著降低。FOXP2的过表达降低了癌症干细胞标志物的表达，从而降低了乳腺癌细胞的乳腺球形成能力。我们发现FOXP2直接抑制Twist1的转录，Twist1是一种促进癌细胞转移和干细胞的原癌基因。在FOXP2过表达的乳腺癌细胞中，Twist1的代偿性表达抵消了FOXP2对乳腺癌细胞干性的抑制作用。总之，结果表明FOXP2通过消除Twist1的转录来减弱乳腺癌细胞的干性。

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引用次数: 0

Elucidation of MMP-9 expression and association of MMP-9 rs3918242–1562 C/T promoter polymorphism in the progression of cervical cancer 宫颈癌进展中MMP-9表达及MMP-9 rs3918242-1562 C/T启动子多态性关联的研究

IF 2.1 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2026-01-16 DOI: 10.1016/j.cancergen.2026.01.008

Pavan Kumar Poleboyina, Smita C. Pawar

This study explores the expression of the MMP-9 gene through transcriptomic analysis and quantitative real-time PCR (qRT-PCR), along with the investigation of the promoter polymorphism rs3918242 (C-1562T) using RFLP, confirmed by Sanger sequencing. A total of 200 samples were analyzed, including 100 cervical squamous cell carcinoma tissues and 100 normal control samples. Results revealed a significant upregulation of MMP-9 mRNA expression in cancerous tissues compared to normal counterparts. Furthermore, analysis of the rs3918242 polymorphism showed a higher prevalence of the C allele among controls, while the T allele was more frequently observed in patients. Notably, individuals with the T/T genotype, under a recessive genetic model, exhibited a significantly increased risk of cervical cancer (p < 0.02; OR = 2.98; 95 % CI: 1.12–7.98). Although no strong association was found between the polymorphism and overall cervical cancer risk, elevated MMP-9 expression was closely linked to disease progression. Transcription factor binding analysis using TRANSFAC revealed that the C-to-T substitution disrupts an SP1 binding site, potentially contributing to increased gene expression. Additionally, assessments of mRNA and pre-mRNA secondary structures indicated that the rs3918242 polymorphism alters RNA conformation, with the C allele displaying higher structural stability than the T allele. These findings suggest that while the polymorphism may not directly confer susceptibility, it could influence gene regulation mechanisms relevant to the development of cervical cancer.

本研究通过转录组学分析和实时荧光定量PCR （qRT-PCR）研究了MMP-9基因的表达，并利用RFLP研究了启动子多态性rs3918242 (C-1562T)， Sanger测序证实了这一点。共分析200例样本，其中宫颈鳞状细胞癌组织100例，正常对照100例。结果显示，与正常组织相比，癌组织中MMP-9 mRNA的表达显著上调。此外，rs3918242多态性分析显示，C等位基因在对照组中患病率较高，而T等位基因在患者中更常见。值得注意的是，在隐性遗传模型下，具有T/T基因型的个体表现出显著增加的宫颈癌风险（p < 0.02; OR = 2.98; 95% CI: 1.12-7.98）。虽然没有发现多态性与总体宫颈癌风险之间的强烈关联，但MMP-9表达的升高与疾病进展密切相关。使用TRANSFAC进行转录因子结合分析发现，C-to-T取代会破坏SP1结合位点，可能导致基因表达增加。此外，对mRNA和mRNA前二级结构的评估表明，rs3918242多态性改变了RNA构象，其中C等位基因比T等位基因表现出更高的结构稳定性。这些发现表明，虽然多态性可能不直接导致易感性，但它可能影响与宫颈癌发展相关的基因调控机制。

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引用次数: 0

Genome-wide cfDNA Methylation Profiling of Pleural Effusion Reveals an Immuno-epigenetic Signature for Differentiating Malignant from Benign Cases 胸膜积液的全基因组cfDNA甲基化谱揭示了区分恶性和良性病例的免疫表观遗传特征

IF 2.1 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2026-01-16 DOI: 10.1016/j.cancergen.2026.01.007

Zuyu Sun , Fudong Xu , Jiemin Chen , Nana Zhang , Fang Luo , Xiaojie Huang , Zichen Liu , Xuya Xing , Kun Li , Xuejing Chen , Lili Zhang , Nanying Che

Background

Distinguishing malignant pleural effusion (MPE) from benign pleural effusion (BPE) remains clinically challenging because conventional cytology has limited sensitivity. We investigated whether cfDNA methylation profiling of pleural effusion supernatant could provide a non‑invasive diagnostic alternative.

Methods

Patients with pleural effusion were consecutively and prospectively recruited from Beijing Chest Hospital between November 2022 and March 2024. We conducted genome-wide cfDNA methylation profiling on qualified pleural effusion samples. A mechanistically relevant diagnostic signature was developed using a knowledge-driven approach, integrating probes involving immune pathways and immune cell deconvolution data from the training set. The final signature's performance was subsequently tested in an internal validation cohort and benchmarked against conventional cytology.

Results

A total of 101 participants were enrolled, including 45 MPE and 56 BPE according to the composite reference standard. We observed a distinct methylation landscape between MPE and BPE, identifying 3,119 hypermethylated and 232 hypomethylated DMPs in MPE that were enriched in immune‑related pathways (such as T cell activation). Deconvolution indicated significant differences in immune cell–derived cfDNA (including CD8+ T cells, B cells, eosinophils) between groups. A 7‑CpG-model based on LASSO classifier achieved an AUC of 0.980 (95% CI: 0.954–1.000) in the training set and 0.963 (95% CI: 0.896–1.000) in the internal validation set. The classifier substantially improved MPE detection in cytology‑negative or indeterminate cases and identified MPEs missed by conventional methods.

Conclusions

A 7‑CpG-model from pleural effusion cfDNA reliably discriminates MPE from BPE and shows promise as a reflex test for resolving cytologic uncertainty.

背景：由于常规细胞学的敏感性有限，区分恶性胸腔积液（MPE）和良性胸腔积液（BPE）在临床上仍然具有挑战性。我们研究了胸腔积液上清cfDNA甲基化谱是否可以提供一种非侵入性的诊断选择。方法于2022年11月至2024年3月在北京胸科医院连续前瞻性招募胸腔积液患者。我们对合格的胸腔积液样本进行了全基因组cfDNA甲基化分析。使用知识驱动的方法，整合涉及免疫途径的探针和来自训练集的免疫细胞反卷积数据，开发了一个机械相关的诊断签名。随后在内部验证队列中测试最终签名的性能，并对常规细胞学进行基准测试。结果共纳入101例受试者，其中MPE 45例，BPE 56例。我们观察到MPE和BPE之间存在明显的甲基化景观，鉴定出MPE中3119个高甲基化和232个低甲基化的dmp，这些dmp富集于免疫相关途径（如T细胞激活）。反褶积显示免疫细胞来源的cfDNA（包括CD8+ T细胞、B细胞、嗜酸性粒细胞）在两组之间存在显著差异。基于LASSO分类器的7 - cpg模型在训练集中的AUC为0.980 (95% CI: 0.954-1.000)，在内部验证集中的AUC为0.963 （95% CI: 0.896-1.000）。该分类器大大提高了细胞学阴性或不确定病例的MPE检测，并识别了传统方法遗漏的MPE。结论胸膜积液cfDNA 7 - cpg模型可可靠地区分MPE和BPE，并有望作为一种解决细胞学不确定性的反射试验。

{"title":"Genome-wide cfDNA Methylation Profiling of Pleural Effusion Reveals an Immuno-epigenetic Signature for Differentiating Malignant from Benign Cases","authors":"Zuyu Sun , Fudong Xu , Jiemin Chen , Nana Zhang , Fang Luo , Xiaojie Huang , Zichen Liu , Xuya Xing , Kun Li , Xuejing Chen , Lili Zhang , Nanying Che","doi":"10.1016/j.cancergen.2026.01.007","DOIUrl":"10.1016/j.cancergen.2026.01.007","url":null,"abstract":"<div><h3>Background</h3><div>Distinguishing malignant pleural effusion (MPE) from benign pleural effusion (BPE) remains clinically challenging because conventional cytology has limited sensitivity. We investigated whether cfDNA methylation profiling of pleural effusion supernatant could provide a non‑invasive diagnostic alternative.</div></div><div><h3>Methods</h3><div>Patients with pleural effusion were consecutively and prospectively recruited from Beijing Chest Hospital between November 2022 and March 2024. We conducted genome-wide cfDNA methylation profiling on qualified pleural effusion samples. A mechanistically relevant diagnostic signature was developed using a knowledge-driven approach, integrating probes involving immune pathways and immune cell deconvolution data from the training set. The final signature's performance was subsequently tested in an internal validation cohort and benchmarked against conventional cytology.</div></div><div><h3>Results</h3><div>A total of 101 participants were enrolled, including 45 MPE and 56 BPE according to the composite reference standard. We observed a distinct methylation landscape between MPE and BPE, identifying 3,119 hypermethylated and 232 hypomethylated DMPs in MPE that were enriched in immune‑related pathways (such as T cell activation). Deconvolution indicated significant differences in immune cell–derived cfDNA (including CD8+ T cells, B cells, eosinophils) between groups. A 7‑CpG-model based on LASSO classifier achieved an AUC of 0.980 (95% CI: 0.954–1.000) in the training set and 0.963 (95% CI: 0.896–1.000) in the internal validation set. The classifier substantially improved MPE detection in cytology‑negative or indeterminate cases and identified MPEs missed by conventional methods.</div></div><div><h3>Conclusions</h3><div>A 7‑CpG-model from pleural effusion cfDNA reliably discriminates MPE from BPE and shows promise as a reflex test for resolving cytologic uncertainty.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"302 ","pages":"Pages 62-72"},"PeriodicalIF":2.1,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Functional impact assessment of tissue-specific missense variants in the PTPRH gene using a multi-tool computational framework 使用多工具计算框架评估PTPRH基因中组织特异性错义变异的功能影响。

IF 2.1 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2026-01-14 DOI: 10.1016/j.cancergen.2026.01.006

Ali Ammar Naseem , Ranjha Khan , Uzma Hameed

Cancer is driven by genetic alterations that disrupt cellular processes, and one key gene involved in this progression is Protein Tyrosine Phosphatase Receptor Type H (PTPRH). Acting as both a tumor suppressor and oncogene, the role of PTPRH varies across cancer types. Mutations in PTPRH can either promote cancer or act as tumor suppressors, depending on the type of tissue in which they occur. This project investigates missense variants of PTPRH using in silico analysis. From the COSMIC database, 478 unique missense variants were identified, with 14 variants consistently predicted as damaging across eight computational tools (fathmm, PROVEAN, PolyPhen-2, SIFT, PANTHER, Align-GVGD, SNPs&GO, and PhD-SNP). These variants were analyzed for their impact on protein stability using several prediction tools (MUpro, I-Mutant, MCSM, Missense3D, SDM, DUET, DynaMut, and ENCoM), with 10 variants showing potential disruption of PTPRH protein stability. Evolutionary conservation analysis revealed high conservation scores for all 14 variants, indicating the structural importance of these variants. The domain profiling also revealed their location in key regions of the protein. The 3D protein structures were constructed by homology modeling using the Swiss-Model server. Further analysis using GeneMANIA and STRING highlighted the broader impacts of these mutations on PTPRH interactions and cellular pathways. Investigating the association of PTPRH mutations with various cancer types using CanSAR.ai, cBioPortal, Kaplan-Meier Plotter, and GEPIA revealed their significance in cancer progression. These findings emphasize the utility of in silico analysis in prioritizing cancer-associated variants and provide a rational foundation for future experimental validation and targeted therapeutic investigation.

癌症是由破坏细胞过程的基因改变驱动的，而参与这一进程的一个关键基因是蛋白酪氨酸磷酸酶受体H型（PTPRH）。作为肿瘤抑制因子和致癌基因，PTPRH的作用因癌症类型而异。PTPRH的突变既可以促进癌症，也可以作为肿瘤抑制因子，这取决于它们发生的组织类型。本项目利用硅分析研究PTPRH的错义变异。从COSMIC数据库中，确定了478个独特的错义变异，其中14个变异在8个计算工具（fathmm， PROVEAN, polyphen2， SIFT， PANTHER, Align-GVGD， snp & go和PhD-SNP）中一致地被预测为破坏性变异。使用几种预测工具（MUpro、I-Mutant、MCSM、Missense3D、SDM、DUET、DynaMut和ENCoM）分析了这些变异对蛋白稳定性的影响，其中10个变异显示出对PTPRH蛋白稳定性的潜在破坏。进化保守分析显示，所有14个变异的保守得分都很高，表明这些变异在结构上的重要性。结构域分析也揭示了它们在蛋白质关键区域的位置。利用Swiss-Model服务器进行同源性建模，构建蛋白的三维结构。使用GeneMANIA和STRING的进一步分析强调了这些突变对PTPRH相互作用和细胞途径的更广泛影响。使用canar研究PTPRH突变与各种癌症类型的关系。ai、cbiopportal、Kaplan-Meier Plotter和GEPIA揭示了它们在癌症进展中的重要性。这些发现强调了计算机分析在癌症相关变异排序中的作用，并为未来的实验验证和靶向治疗研究提供了合理的基础。

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引用次数: 0

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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