Frontiers in Genetics最新文献

{"title":"Case Report: A novel intronic variant of <i>NIPBL</i> gene detected in a child with cornelia de lange syndrome.","authors":"Xiao Ting Shao, Yu Xuan Dai, Yu Fang Zhao, Yu Hang Chen, Ling Jing Ying","doi":"10.3389/fgene.2025.1665167","DOIUrl":"10.3389/fgene.2025.1665167","url":null,"abstract":"<p><strong>Background: </strong>Cornelia de Lange syndrome (CdLS) is a genetically heterogeneous disorder involving multi-system organs, causing physical and mental congenital malformation. Nipped-B-like protein (<i>NIPBL</i>) variants are associated with various CdLS phenotypes. Newborns with typical clinical manifestations (intellectual disability, special appearances, and limb malformation) require a diagnosis. However, diagnosing CdLS is challenging on account of its heterogeneity of genotype and phenotype.</p><p><strong>Methods: </strong>In this study, molecular analysis was applied, containing whole exome sequencing (WES), reverse transcriptase PCR (RT-PCR), and minigene splicing assays.</p><p><strong>Results: </strong>We identified a novel splice-donor variant (<i>NIPBL</i> c.6343 + 1G>A) by WES. RT-PCR and minigene splicing assays were performed to identify the function of the splice-donor variant on subsequent RNA splicing. The variant caused exon 36 to be skipped. A premature termination codon (PTC) appeared subsequently and a truncated protein with a length of 2088 aa was produced.</p><p><strong>Conclusion: </strong>A novel pathogenic variant of CdLS is identified, which affects normal mRNA splicing of the <i>NIPBL</i> gene. These findings enrich the knowledge of CdLS gene variants, which may be responsible for developing this rare disease.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1665167"},"PeriodicalIF":2.8,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12457154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Identification and functional characteristics of a novel splice site variant in <i>L1CAM</i> caused X-linked hydrocephalus.","authors":"Shijie Zhou, Hao Zhang, Xue Li, Quan Chen, Zhihong Xu","doi":"10.3389/fgene.2025.1676267","DOIUrl":"https://doi.org/10.3389/fgene.2025.1676267","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fgene.2025.1588709.].</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1676267"},"PeriodicalIF":2.8,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diphenyl pyridine intervention improves <i>S. aureus</i>-induced pneumonia by globally regulating transcriptome profile.","authors":"Wei Duan, Qingfeng Zhu, Hai Ci, Jingang Zhang, Zhiwei Tian, Wanyu Li, Zhengfu Yang","doi":"10.3389/fgene.2025.1624327","DOIUrl":"10.3389/fgene.2025.1624327","url":null,"abstract":"<p><strong>Background: </strong>Pneumonia, induced by various bacteria or viruses, is a globally prevalent inflammatory disease that threatens the life of millions of people. <i>Staphylococcus aureus</i> (<i>S. aureus</i>) is a major pathogen of pneumonia and can be inhibited by Diphenyl pyrimidine (DP), while the underlying mechanisms are largely unknown.</p><p><strong>Methods: </strong>In this study, we conducted the <i>S. aureus</i>-induced rat pneumonia model and then performed DP treatment to inhibit the injury. Meanwhile, whole transcriptome sequencing (RNA-seq) experiment was performed to identify the dysregulated genes with expression and alternative splicing changes, as well as their enriched functions. Hub genes and immune cell proportion changes by DP were also identified to explore the underlying mechanism.</p><p><strong>Results: </strong>We identified 2,225 up and 1,257 down DEGs between DP and SA samples, and found they were significantly enriched in immune and inflammatory response pathways, as well as angiogenesis and apoptosis pathways. At the same time, DP treatment also significantly altered the alternative splicing profile, including 3898 AS genes and 416 co-regulated genes with DEGs. Functional analysis of co-regulated genes demonstrated they were enriched in immune response, signal transduction, and apoptosis regulation pathways. Finally, we identified ten hub genes by protein-protein network analysis from DEGs, including CCNA2, TOP2A, CDK1, ESPL1, KIF2C, PBK, UHRF1, RACGAP1, PCLAF, and RAD51 that were totally repressed by DP treatment.</p><p><strong>Conclusion: </strong>In summary, our study demonstrated that DP treatment can profoundly modulate the immune and inflammatory response by regulating the transcriptome profile of peripheral blood monocytes (PBMCs). The identified hub genes by DP treatment are potential therapeutic targets for <i>S. aureus</i>-induced pneumonia in future.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1624327"},"PeriodicalIF":2.8,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12457106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of NR3C1 as a methylation marker for the prevention and treatment of gastric cancer in Rhizoma Atractylodis Macrocephalae based on machine learning algorithm and bioinformatics analysis.","authors":"Shicong Huang, Qian Gu, Yan Chen, Xiaofang Huang, Yuhua Du, Ziying Zhou, Yi Nan, Ling Yuan","doi":"10.3389/fgene.2025.1584986","DOIUrl":"10.3389/fgene.2025.1584986","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study was to identify the markers of Rhizoma Atractylodis Macrocephalae (RAM) for the prevention and treatment of gastric cancer using bioinformatics analysis.</p><p><strong>Methods: </strong>The main active components of RAM were screened using the Traditional Chinese Medicine Systematic Pharmacology Profiling Platform (TCMSP) and SwissADME, the target genes of RAM were screened using WGCNA and three machine learning algorithms, and the target genes were analyzed clinically and by methylation.</p><p><strong>Results: </strong>Three core genes, namely, CA2, HSP90AA1, and NR3C1, were screened by WGCNA and three machine learning algorithms. Clinical correlation analysis and epigenetic analyses showed that these genes play the most important role in gastric cancer. In gastric cancer, there was a strong correlation between NR3C1 methylation and its mRNA expression, suggesting that methylation of NR3C1 may be involved in the regulation of its expression. Therefore, methylation correlation analysis of NR3C1 was performed, and it was found that the methylation type of NR3C1 was mainly m6A methylation; the frequency of methylation hypermutation in the CDS region was also high, and the homologous region and the promoter of the NR3C1 gene showed hypomethylation and hypermethylation differences in the analyses of gastric tissues, races, and gastric cancer subtypes, respectively. Among the methylated peninsular mutations, the TSS200; 5'UTR, 5'UTR, and TSS1500; 5'UTR regions were statistically significant.</p><p><strong>Conclusion: </strong>NR3C1 can be used as a potential methylation marker of RAM for the prevention and treatment of gastric cancer.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1584986"},"PeriodicalIF":2.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic heterogeneity in childhood leukemia/lymphoma: a Turkish cohort with strong predisposition.","authors":"Gizem Onder, Ozkan Ozdemir, Fulya Taylan, Cengiz Canpolat, Koray Yalcin, Fatih Erbey, Banu Oflaz Sozmen, Fikret Asarcikli, Turan Bayhan, Yunus Murat Akcabelen, Nese Yarali, Namik Yasar Ozbek, Ikbal Ok Bozkaya, Dilek Kacar, Berk Ergun, Alper Akkus, Davut Albayrak, Elif Ince, Ugur Demirsoy, Gul Nihal Ozdemir, Omer Dogru, Seda Aras, Eylul Aydin, Busra Unal, Ufuk Amanvermez, Ozlem Akgun Dogan, Sezer Akyoney, Muge Sayitoglu, Ann Nordgren, Nihat Bugra Agaoglu, Ugur Ozbek, Ozden Hatirnaz Ng","doi":"10.3389/fgene.2025.1624306","DOIUrl":"10.3389/fgene.2025.1624306","url":null,"abstract":"<p><strong>Background: </strong>Leukemia is the most common cancer in children, and 10%-15% of patients with leukemia/lymphoma carry pathogenic germline cancer-predisposing variants. Identifying these variants is critical for understanding the genetic predisposition and optimizing clinical management.</p><p><strong>Methods: </strong>We performed germline short-read sequencing in 36 individuals from 20 families with suspected leukemia/lymphoma predisposition, including 20 index cases, 9 affected relatives, and 7 unaffected members.</p><p><strong>Results: </strong>We identified 13 clinically relevant germline variants in known cancer predisposition genes including <i>TP53, ETV6, MSH6, MLH1,</i> and <i>BRCA1</i>. Notably, we uncovered novel candidate variants in <i>ATR, TNFRSF9, ETAA1</i>, and <i>KSR1</i>, which was supported by segregation analysis, consanguinity patterns, and secondary malignancy phenotypes. Several index cases exhibited striking familial cancer syndromes involving both hematologic and solid tumors, with progression from ALL to AML or glioma. Deep clinical-genomic correlation enabled reclassification of variants and refined diagnostic and therapeutic decision-making in multiple cases. The patients were referred to genetic counseling for surveillance of carriers and risk assessment for various family members.</p><p><strong>Conclusion: </strong>These findings emphasize the clinical utility of germline testing in pediatric hematologic cancers by providing novel insights into the predisposition to leukemia/lymphoma and contributing to treatment regimens, donor selection, and diagnostic refinement, particularly in populations with high consanguinity.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1624306"},"PeriodicalIF":2.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12454056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZC3H18 regulates alternative splicing and related genes in cervical cancer.","authors":"Wenjuan Chen, Chenying Liu, Siyi Li, Xingyun Xie, Dan Hu, Yaobin Lin","doi":"10.3389/fgene.2025.1621238","DOIUrl":"10.3389/fgene.2025.1621238","url":null,"abstract":"<p><strong>Introduction: </strong>Alternative splicing (AS) and RNA-binding proteins (RBPs) have been implicated in various diseases. However, a comprehensive understanding of their role in RNA metabolism, progression, and metastasis in cervical cancer remains elusive. This study aimed to identify the potential effect of zinc finger CCCH-type containing 18 (ZC3H18) in cervical cancer.</p><p><strong>Methods: </strong>The Gene Expression Omnibus (GEO) dataset (GSE94427) was used to analyze the expression level of ZC3H18 in HeLa cells and its regulated alternative splicing events (ASEs). The Cancer Genome Atlas (TCGA) cervical cancer dataset and in vitro experiments were used for verification. The signaling pathways and functions of ZC3H18-regulated ASEs were investigated through enrichment analysis.</p><p><strong>Results: </strong>Knockdown of ZC3H18 in HeLa cells increased the expression of 106 genes but decreased the expression of 226 genes. ZC3H18 was found to be involved in the regulation of 1,830 ASEs. The AS genes were enriched in cervical cancer-related signaling pathways. Validation using 39 cervical cancer samples from the TCGA database showed that 20 cases had low ZC3H18 expression and 19 had high expression. By integrating GEO and TCGA datasets along with in vitro experiments, 18 ASEs with consistent changes were identified.</p><p><strong>Discussion: </strong>This study demonstrated that ZC3H18 extensively regulates AS of cancer-associated pathways in HeLa cells and cervical cancer tissues. The identification of ZC3H18-regulated ASEs may provide potential targets for cervical cancer treatment.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1621238"},"PeriodicalIF":2.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12454084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms and recent advances in non-coding RNAs and RNA modifications in antiplatelet drug resistance.","authors":"Ping Ni, Kejie Chen, Jing Xiang, Haifeng Shao, Xiaoling Chen, Qiao Chen, Lingling Wang, Junli Hao, Xinyi Huang, Qing Cao, Yali Yang, Quandan Tan, Jie Yang, Suping Li","doi":"10.3389/fgene.2025.1618105","DOIUrl":"10.3389/fgene.2025.1618105","url":null,"abstract":"<p><p>The high incidence and mortality rates of cardiovascular and cerebrovascular diseases make them a significant global health challenge. Antiplatelet drugs play a central role in the prevention and treatment of these diseases. Despite the wide range of available antiplatelet drugs, antiplatelet drug resistance is not rare. So optimizing drug use through personalized treatment strategies to achieve maximum therapeutic benefit remains a major challenge in clinical practice. Non-coding RNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have made significant progress in understanding their regulatory roles in drug resistance, becoming a frontier area of current research. In addition to the regulatory functions of non-coding RNAs, emerging studies have highlighted the role of RNA modifications, such as N6-methyladenosine (m6A), in the regulation of gene expression and cellular processes involved in antiplatelet drug resistance. These modifications contribute to the stability, splicing, and translation of RNA, further influencing their roles in drug resistance mechanisms. In recent years, significant progress has been made in the research of non-coding RNAs and RNA modifications, revealing their crucial roles in the mechanisms of antiplatelet drug resistance. This review focuses on the latest advancements in non-coding RNA research related to antiplatelet drug resistance and explores the emerging field of RNA modifications. It analyzes potential underlying mechanisms and discusses future research directions, aiming to provide new theoretical support and research perspectives for personalized precision antiplatelet.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1618105"},"PeriodicalIF":2.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive analysis and validation of angiogenesis in vascular dementia from the perspective of diagnosis, prevention, and treatment.","authors":"Lijun Xu, Yujiao Wang, Daojun Xie","doi":"10.3389/fgene.2025.1646991","DOIUrl":"10.3389/fgene.2025.1646991","url":null,"abstract":"<p><strong>Background: </strong>Angiogenesis is a critical pathological process in vascular dementia (VD), yet current therapeutic strategies targeting this mechanism remain limited. Identifying novel molecular pathways involved in angiogenesis holds significant promise for advancing both diagnostic and therapeutic approaches for VD.</p><p><strong>Methods: </strong>We first applied weighted gene coexpression network analysis (WGCNA) and differentially expressed gene (DEG) analysis, combined with phenotypic gene database mining, to identify angiogenesis-associated genes in VD. We then used the Least Absolute Shrinkage and Selection Operator (LASSO) regression to select key diagnostic genes. The diagnostic efficacy of these genes was evaluated using receiver operating characteristic (ROC) curve analysis, while their association with immune cell infiltration was assessed via xCell immunoinfiltration. Using single-nucleus RNA sequencing (snRNA-seq), we determined the cellular distribution of key genes and applied Gene Set Enrichment Analysis (GSEA) to analyze functional pathways in the differentially expressed cell clusters. Finally, we validated gene expression changes in the hippocampus of bilateral common carotid artery occlusion (BCCAO)-induced VD rats using quantitative polymerase chain reaction (qPCR) and Western blot (WB).</p><p><strong>Results: </strong>Ultimately, we screened five key genes, namely, <i>CCL2</i>, <i>VEGFA</i>, <i>SPP1</i>, <i>ANGPT2</i>, and <i>ANGPTL4</i>, which were all downregulated in the BCCAO model. The results of snRNA-seq showed that key genes were mainly clustered in microglia, endothelial cells, and astrocytes. Microglia, endothelial cells, and astrocytes play a key role in regulating angiogenesis.</p><p><strong>Conclusion: </strong>These five key genes might be used as angiogenesis diagnostic genes for VD and might be novel potential targets for diagnosis, treatment, and prevention.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1646991"},"PeriodicalIF":2.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A lipid metabolism and lysosome-based risk signature for prognosis and immune response prediction in uterine corpus endometrial carcinoma.","authors":"Yuanyuan Zhu, Pusheng Yang, Shu Zhang","doi":"10.3389/fgene.2025.1594682","DOIUrl":"10.3389/fgene.2025.1594682","url":null,"abstract":"<p><strong>Background: </strong>The dysregulation of genes related to lipid metabolism and lysosomal function has been reported to significantly contribute to tumor progression. In this study, we systematically explored the roles played by lipid metabolism and lysosomes in uterine corpus endometrial carcinoma (UCEC), aiming to identify potential biomarkers for predicting prognosis and immune checkpoint therapy efficacy.</p><p><strong>Methods: </strong>Genes associated with lipid metabolism and lysosomal function were retrieved from the MSigDB and GO databases. Transcriptomic data and clinical information of patients were acquired from The Cancer Genome Atlas database. A prognostic model was constructed using consensus clustering, univariate Cox regression, and LASSO regression. ROC curves, Kaplan-Meier plots, and calibration curves were employed to assess the predictive capacity of the model, while ssGSEA, TIDE, and IPS were used to evaluate the response of high- and low-risk groups to immunotherapy. Drug sensitivity was assessed with the \"oncoPredict\" R package. Given that we identified a strong association between <i>PLAAT1</i> and CD8⁺ T-cell infiltration, this gene was selected for loss-of-function assays in UCEC cells, including the evaluation of their proliferative, invasive, and migratory potential.</p><p><strong>Results: </strong>An eight-gene (<i>LAMP3</i>, <i>RNF183</i>, <i>EEF1A2</i>, <i>PLAAT1</i>, <i>ELAPOR1</i>, <i>B4GALT1</i>, <i>ATP10B</i>, and <i>PLA2G10</i>) risk signature based on lipid metabolism and lysosomal function was constructed to distinguish high-risk and low-risk UCEC patients. Subsequent analyses showed that patients classified as high risk had higher TIDE scores, whereas those categorized as low risk exhibited higher MSI scores and greater levels of CD8⁺ T-cell infiltration. All evidence suggested that patients in the low-risk group displayed greater immunogenicity and sensitivity to both immunotherapy and chemotherapy. Analysis using the TIMER database indicated that among the eight risk genes, <i>PLAAT1</i> showed the strongest association with CD8⁺ T-cell immune infiltration in UCEC. Cytological experiments confirmed that the knockdown of <i>PLAAT1</i> effectively suppressed the proliferation and motility of endometrial cancer cells.</p><p><strong>Conclusion: </strong>We constructed a risk prognostic model for UCEC based on a combination of lysosomal- and lipid metabolism-related genes. Our findings highlight the oncogenic potential of PLAAT1 in endometrial cancer and provide novel insights into the diagnosis and therapy of this cancer type.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1594682"},"PeriodicalIF":2.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Constructing a neutrophil extracellular trap model based on machine learning to predict clinical outcomes and immune therapy responses in oral squamous cell carcinoma.","authors":"Jian Wang, Zhenzhen Li, Zhiwei Li, Zijing Yu, Wenpin Xu","doi":"10.3389/fgene.2025.1616868","DOIUrl":"10.3389/fgene.2025.1616868","url":null,"abstract":"<p><strong>Background: </strong>Neutrophil extracellular traps (NETs) represent a novel form of inflammatory cell death in neutrophils. Recent studies suggest that NETs can promote cancer progression and metastasis through various mechanisms. This study focuses on identifying prognostic NETs signatures and therapeutic targets for oral squamous cell carcinoma (OSCC).</p><p><strong>Materials and methods: </strong>We performed non-negative matrix factorization (NMF) analysis on 89 previously reported NET-related genes within the TCGA cohort. Subsequent analysis of subtype feature genes was conducted using the weighted gene co-expression network analysis (WGCNA). Six machine learning algorithms were employed for model training, with the best model selected based on 1-year, 3-year, and 5-year AUC values. A NETs signature was developed to predict overall survival in OSCC patients. Multi-omics validation was carried out, and stable knockout OSCC cell lines for key genes were established to assess the biological functions of LINC00937 <i>in vitro</i>.</p><p><strong>Results: </strong>Five NETs-related clusters were identified in OSCC patients, with the C5 subtype showing the most favorable prognosis. The WGCNA network revealed 443 characteristic genes. The Enet algorithm exhibited optimal performance in providing a predictive NETs signature. Multi-omics analysis indicated that NETs signaling is linked to an immunosuppressive microenvironment and can predict the efficacy of immunotherapy. <i>In vitro</i> experiments confirmed that knocking down LINC00937 led to inhibited tumor growth.</p><p><strong>Conclusion: </strong>This study highlights the emerging role of NETs in OSCC, presenting a prognostic NETs feature and identifying LINC00937 as a significant factor in OSCC. These findings contribute to risk stratification and the discovery of new therapeutic targets for OSCC patients.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1616868"},"PeriodicalIF":2.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}