Frontiers in Genetics最新文献

{"title":"IGF-1 secreted by mesenchymal stem cells affects the function of lymphatic endothelial progenitor cells: a potential strategy for the treatment of lymphedema.","authors":"Zekuan Xue, Dongdong Yang, Zhiwei Jin, Yijie Li, Yunfei Yu, Xinchun Zhao, Yongzhou Huang, Shengqiu Jia, Tong Zhang, Guilin Huang, Jixue Hou","doi":"10.3389/fgene.2025.1584095","DOIUrl":"10.3389/fgene.2025.1584095","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) can participate in lymphangiogenesis through paracrine effects, while lymphatic endothelial progenitor cells (LEPCs), a subpopulation of endothelial progenitor cells (EPCs), can differentiate into mature lymphatic endothelial cells, thereby influencing lymphatic function. In the present study, we investigated the mechanism by which MSCs regulate the activity of LEPCs through paracrine effects and preliminarily explored the possibility of the two types of cells working together to treat lymphovascular diseases. After isolation of MSCs and LEPCs from the bone marrow of C57BL/6 J mice, <i>in vitro</i> experiments verified that insulin-like growth factor 1 (IGF-1) secreted by MSCs activated the PI3K/Akt/mTOR pathway to promote the proliferation of LEPCs; IGF-1 decreased the rate of apoptosis and affected the cycle progression of LEPCs and the nucleotide metabolism levels. The therapeutic efficacy of combined transplantation of MSCs and LEPCs was shown to be superior to that of transplantation of LEPCs alone in murine hindlimb lymphedema models. These results suggest that MSCs significantly promote the proliferation of LEPCs through the activation of the PI3K/Akt/mTOR pathway in LEPCs by secreting IGF-1, and that IGF-1 also inhibits apoptosis and regulates cell metabolism. Combined transplantation of MSCs and LEPCs provides an experimental rationale and potential strategy for cell therapy in lymphedema.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1584095"},"PeriodicalIF":2.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12133893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225218","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":"Impact of ITH on PRAD patients and feasibility analysis of the positive correlation gene MYLK2 applied to PRAD treatment.","authors":"Chuanyu Ma, Guandu Li, Xiaohan Song, Xiaochen Qi, Tao Jiang","doi":"10.3389/fgene.2025.1589259","DOIUrl":"10.3389/fgene.2025.1589259","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Prostate adenocarcinoma (PRAD) is an extremely widespread site of urological malignancy and is the second most common male cancer in the world. Currently, research progress in immunotherapy for prostate treatment is slower compared to other tumours, which is mainly considered to be caused by the low rate of immune response in prostate cancer as a cold tumour. Recent studies have shown that intra-tumour heterogeneity (ITH) is an important impediment to PRAD immunotherapy. Therefore, we set out to investigate the feasibility of judging patients' disease and knowing the clinical treatment based on the level of ITH.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Clinical information and transcriptome expression matrices of PRAD samples were gained from The Cancer Genome Atlas (TCGA) database. The ITH-score of PRAD samples was evaluated using the DEPTH algorithm. The optimal cut-off value of RiskScore was calculated based on the difference in survival curves, and PRAD patients were classified into high ITH and low ITH groups based on the optimal cut-off value. Genes with expression differences were screened by differential expression gene analyses (DEGs), and 103 positively correlated differentially expressed genes were identified based on these genes as well as the ITH-score. We conducted multivariate Cox regression to sift for prognostically relevant genes to structure an ITH-related prognostic signature. GO and KEGG pathway enrichment analyses were performed on these 103 positively correlated differentially expressed genes, and the proportion and type of tumour-infiltrating immune cells were assessed by TIMER, CIBERSORT, CIBERSORT-ABS, QUANTISEQ, MCPCOUNTER, XCELL and EPIC algorithms in patients. In addition, we calculated the relevance of immunotherapy and predicted various drugs that might be used for treatment and evaluated the predictive power of survival models under multiple machine learning algorithms through the training set TCGA-PRAD versus the validation set PRAD-FR cohort. Based on the upregulated differential gene and ITH-score correlation ranking, combined with the prognostic performance of the gene, we chose MYLK2 as an elite gene for ITH, and performed cellular experiments to validate it by PCR and WB, as well as CCK8, scratch experiments, and transwell experiments on si-MYLK2 PRAD. Finally, we constructed cox regression models as well as random forest survival models based on the expression levels of SYNPO2L, MYLK2, CKM and MYL3.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We found that lowering the ITH-score resulted in better survival outcomes. We identified 20 highly correlated differentially expressed genes by calculating the correlation coefficient (cor&gt;0.3) between them by DEGs as well as ITH-score, and selected four genes with p-value less than 0.05 (SYNPO2L, MYLK2, CKM and MYL3) by combining with cox regression. Survival analysis based on the differential expression grouping of SYNPO2L, MYLK2, CKM and MYL3 suggested s","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1589259"},"PeriodicalIF":2.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215650","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":"Editorial: A year in review: discussions in human and medical genomics.","authors":"Maxim B Freidin, Jared C Roach","doi":"10.3389/fgene.2025.1618183","DOIUrl":"10.3389/fgene.2025.1618183","url":null,"abstract":"","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1618183"},"PeriodicalIF":2.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215649","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":"Lack of association between genetic variations in <i>CYP3A5</i> and blood pressure or hypertension risk in the UK biobank.","authors":"Pia Leibold, Christelle Lteif, Julio D Duarte","doi":"10.3389/fgene.2025.1490863","DOIUrl":"10.3389/fgene.2025.1490863","url":null,"abstract":"<p><strong>Introduction: </strong>Hypertension (HTN) is a leading risk factor for several cardiovascular diseases. While some previous studies reported that <i>CYP3A5</i> variants were associated with decreased blood pressure and risk of HTN, others reported no associations. Therefore, we aimed to analyze these associations in the UK Biobank, a population large enough to have sufficient power to detect meaningful associations.</p><p><strong>Methods: </strong>The association of <i>CYP3A5</i> variants (<i>*3</i>, <i>*6</i>, <i>*7</i>) and CYP3A5 activity with systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and HTN diagnosis was analyzed in the UK Biobank (N = 487,171). Linear and logistic regression models were used, adjusting for age, sex, race, antihypertensives use, smoking status, and salt intake. Moreover, subgroup analyses were performed in Black participants, White participants, participants of East Asian and South Asian descent separately, using the same models.</p><p><strong>Results: </strong>Neither the CYP3A5 variants, nor the CYP3A5 activity showed significant associations with SBP, DBP, MAP, or HTN. In a sensitivity analysis based on different racial subgroups, only White participants showed significant associations between the <i>CYP3A5*3</i> variant and slightly higher DBP (β = 0.10 mmHg, 95% CI: 0.02 to 0.18, <i>P</i> = 0.01), as well as between genotype-predicted CYP3A5 activity score and slightly lower DBP (β = -0.10 mmHg, 95% CI: -0.18 to -0.02, <i>P</i> = 0.01).</p><p><strong>Discussion: </strong>While some associations were statistically significant, the small effect sizes and lack of associations observed in the whole UK Biobank population suggest that <i>CYP3A5</i> variation likely has no impact on blood pressure related phenotypes in a general population.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1490863"},"PeriodicalIF":2.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215651","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":"<i>IFI35</i> and <i>IFIT3</i> are potentially important biomarkers for early diagnosis and treatment of esophageal squamous cell carcinoma: based on WGCNA and machine learning analysis.","authors":"Hao Wu, Liang Yang, Xiaokun Weng","doi":"10.3389/fgene.2025.1583202","DOIUrl":"10.3389/fgene.2025.1583202","url":null,"abstract":"<p><strong>Background: </strong>Esophageal squamous cell carcinoma (ESCC) does not have distinct and highly sensitive biomarkers, making its diagnosis difficult. Consequently, identifying dependable biomarkers is critical, as these indicators can facilitate accurate ESCC diagnosis and enable effective prognostic evaluation.</p><p><strong>Methods: </strong>ESCC datasets (GSE29001, GSE20347, GSE45670, and GSE161533) were sourced from the GEO, and the Limma package identified differentially expressed genes (DEGs). To characterize co-expression network, weighted gene co-expression network analysis (WGCNA) was performed, allowing for the identification of relevant co-expression modules. To assess the biological pathways of intersecting genes, we performed pathway enrichment analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). The Support Vector Machine Recursive Feature Elimination (SVM), along with Least Absolute Shrinkage and Selection Operator (LASSO) regression, was applied to identify clinical biomarkers. Finally, the differences of immune cell infiltration were also detected.</p><p><strong>Results: </strong>1,019 genes were derived by integrating DEGs with co-expressed module genes. KEGG and GO revealed a strong association between these genes and processes such as chemotaxis and IL-17 signaling pathways. Two hub genes (<i>IFIT3</i> and <i>IFI35</i>) were selected through LASSO regression and SVM. Additionally, ROC curve analysis confirmed their potential for reliable diagnostic performance. Furthermore, differences in immune cell infiltration were observed.</p><p><strong>Conclusion: </strong>Collectively, <i>IFIT3</i> and <i>IFI35</i> emerged as promising candidate biomarkers, offering novel insights to enhance early detection and guide targeted treatment strategies for ESCC.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1583202"},"PeriodicalIF":2.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215648","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":"Evaluating the therapeutic potential of BSA-reduced mussel-derived selenium nanoparticles to mitigate copper sulfate-induced hepatic damage and neurodegeneration in a zebrafish model.","authors":"Suganiya Umapathy, Ieshita Pan","doi":"10.3389/fgene.2025.1522370","DOIUrl":"10.3389/fgene.2025.1522370","url":null,"abstract":"<p><strong>Introduction: </strong>Liver fibrosis is the abnormal accumulation of extracellular matrix and eventual formation of fibrous scar in response to chronic liver injury, which can be triggered by increased levels of reactive oxygen species. The brain-liver axis is a crucial communication pathway that significantly influences the intricate interactions between hepatic function and brain health. Selenium, as a source of selenoproteins, plays a vital role in antioxidant defense systems. The extraction of selenium from mussels leverages their natural bioaccumulation, providing a biocompatible source. Selenium nanoparticles are known for their potential antioxidant activity and can be employed to regulate ROS levels to overcome hepatic damage.</p><p><strong>Methods: </strong>Selenium nanoparticles were synthesized from mussel-extracted selenium and stabilized with bovine serum albumin. The zebrafish models exposed to copper sulfate were treated with selenium nanoparticles (5-25 μg/ml). This study evaluated their potential role as antioxidants against hepatic damage induced by copper sulfate <i>in vivo</i> in the zebrafish model.</p><p><strong>Results: </strong>The bovine serum albumin stabilized selenium nanoparticles reduced for 30 minutes and 1 hour were spherical with a size of 19 and 16 nm. Stabilized selenium nanoparticles reduced for 30 minutes (25 μg/ml) showed significant <i>in vitro</i> reactive oxygen species scavenging activity and improved <i>in vivo</i> antioxidant enzyme levels by decreasing lipid peroxidation and nitric oxide levels. Histopathological examination revealed a delay in the progression of copper sulfate-induced hepatic damage, and upregulated the expression of antioxidants, while the hepatic and mitochondrial damage markers were downregulated.</p><p><strong>Conclusion: </strong>In conclusion, bovine serum albumin-reduced selenium nanoparticles can be a promising therapeutic antioxidant for protecting against reactive oxygen species-induced hepatic damage and neurodegeneration.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1522370"},"PeriodicalIF":2.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208353","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":"Cognitive decline in an adult with ATR-16 syndrome due to an unbalanced translocation between 11p15.5 and 16p13.3: a case report.","authors":"Angela Krutish, Rebekah Kukurudz-Gorowski, Felippe Borlot, Patrick Frosk, Cheryl Rockman-Greenberg, Aizeddin A Mhanni","doi":"10.3389/fgene.2025.1595298","DOIUrl":"10.3389/fgene.2025.1595298","url":null,"abstract":"<p><strong>Background: </strong>Chromosome 16p13.3 deletions cause a contiguous gene deletion syndrome, ATR-16 syndrome. The classic phenotype of ATR-16 syndrome includes either alpha-thalassemia trait or hemoglobin H disease and intellectual disability; however, considerable variable expressivity has been reported with some patients having only an alpha-thalassemia disorder and others exhibiting a more severe phenotype with additional features.</p><p><strong>Case presentation: </strong>We describe an adult male with ATR-16 syndrome (due to an unbalanced <i>de novo</i> translocation involving chromosomes 11p15.5 and 16p13.3) who developed cognitive decline and increasing dyskinetic movements in his late twenties. Biochemical investigations and exome sequencing did not elucidate an alternative explanation for this decline. Furthermore, neither the deletion on chromosome 16 nor the duplication on chromosome 11 encompassed genes that could explain the decline.</p><p><strong>Conclusion: </strong>While cognitive decline has not been previously reported in ATR-16 syndrome, this may be another feature of the condition that is subject to variable expressivity. Taking this together with the apparent increased prevalence of dementia in other neurodevelopmental conditions, we hypothesize that individuals with ATR-16 syndrome may be predisposed to early cognitive decline.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1595298"},"PeriodicalIF":2.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208417","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":"Normal hearing function genetics: have you heard all about it? An integrated approach of genome-wide association studies and transcriptome-wide association studies in three Italian cohorts.","authors":"Aurora Santin, Giulia Pianigiani, Alessandro Gialluisi, Alessandro Pecori, Beatrice Spedicati, Simona Costanzo, Mariarosaria Persichillo, Francesca Bracone, Giuseppe Giovanni Nardone, Paola Tesolin, Stefania Lenarduzzi, Anna Morgan, Amalia De Curtis, Wouter van der Valk, Francis Rousset, Marta Roccio, Heiko Locher, Licia Iacoviello, Maria Pina Concas, Giorgia Girotto","doi":"10.3389/fgene.2025.1522338","DOIUrl":"10.3389/fgene.2025.1522338","url":null,"abstract":"<p><strong>Introduction: </strong>Deepening the genetic mechanisms underlying Normal Hearing Function (NHF) has proven challenging, despite extensive efforts through Genome-Wide Association Studies (GWAS).</p><p><strong>Methods: </strong>NHF was described as a set of nine quantitative traits (i.e., hearing thresholds at 0.25, 0.5, 1, 2, 4, and 8 kHz, and three pure-tone averages of thresholds at low, medium, and high frequencies). For each trait, GWAS analyses were performed on the Moli-sani cohort (n = 1,209); then, replication analyses were conducted on Carlantino (CAR, n = 261) and Val Borbera (VBI, n = 425) cohorts. Expression levels of the most significantly associated genes were assessed employing single-nucleus RNA sequencing data (snRNA-seq) on human fetal and adult inner ear tissues. Finally, for all nine NHF traits, Transcriptome-Wide Association Studies (TWAS) were performed, combining GWAS summary statistics and pre-computed gene expression weights in 12 brain tissues.</p><p><strong>Results: </strong>GWAS on the Discovery cohort allowed the detection of 667 SNPs spanning 327 protein coding genes at a <i>p</i> < 10^-5, across the nine NHF traits. Two loci with a p < 5 × 10^-8 were replicated: 1. rs112501869 within <i>SLC1A6</i> gene, encoding a brain high-affinity glutamate transporter, reached <i>p</i> = 6.21 × 10^-9 in the 0.25 kHz trait. 2. rs73519456 within <i>ASTN2</i> gene, encoding the Astrotactin protein 2, reached genome-wide significance in three NHF traits: 0.5 kHz (<i>p</i> = 1.86 × 10^-8), PTAL (<i>p</i> = 9.40 × 10^-9), and PTAM (<i>p</i> = 3.64 × 10^-8). SnRNA-seq data analyses revealed a peculiar expression of the <i>ASTN2</i> gene in the neuronal and dark cells populations, while for <i>SLC1A6</i> no significant expression was detected. TWAS analyses detected that the <i>ARF4-AS1</i> gene (eQTL: rs1584327) was statistically significant (<i>p</i> = 4.49 × 10^-6) in the hippocampal tissue for the 0.25 kHz trait.</p><p><strong>Conclusion: </strong>This study took advantage of three Italian cohorts, deeply characterized from a genetic and audiological point of view. Bioinformatics and biostatistics analyses allowed the identification of three novel candidate genes, namely, <i>SLC1A6, ASTN2,</i> and <i>ARF4-AS1</i>. Functional studies and replication in larger and independent cohorts will be essential to confirm the biological role of these genes in regulating hearing function; however, these results confirm GWAS and TWAS as powerful methods for novel gene discovery, thus paving the way for a deeper understanding of the entangled genetic landscape underlying the auditory system.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1522338"},"PeriodicalIF":2.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208354","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":"Analysis of the correlation between RFC4 expression and tumor immune microenvironment and prognosis in patients with cervical cancer.","authors":"Bifen Huang, Jianqing Zheng, Bizhen Chen, Min Wu, Lihua Xiao","doi":"10.3389/fgene.2025.1514383","DOIUrl":"10.3389/fgene.2025.1514383","url":null,"abstract":"<p><strong>Background: </strong>Replication factor C subunit 4 (RFC4) plays a critical role in the initiation and progression of some cancers; however, its relationship with tumor-infiltrating immune cells in cervical cancer (CC) has not been comprehensively analyzed. This study aimed to determine whether RFC4 overexpression affects overall survival in CC and to explore its impact and potential mechanisms on the tumor immune microenvironment.</p><p><strong>Methods: </strong>Data from Genotype-Tissue Expression database (GTEx) and Cancer Genome Atlas (TCGA) database were used as the exploration set. Datasets from the Gene Expression Omnibus (GEO) were used as the validation set. We also validated the expression of the RFC4 protein in the Human Protein Atlas (HPA) database and a real cohort. Clinical data on CC were evaluated for their association with RFC4 using TCGA and GEO databases. Possible relationships amongst RFC4, immune cells, and related genes were investigated using Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression (ESTIMATE). GO and KEGG pathway enrichment analyses were used to explore potential mechanisms. Tumor immune dysfunction and exclusion (TIDE) scores were used to predict the immunotherapeutic response to RFC4.</p><p><strong>Results: </strong>In the exploration, validation, and real cohort datasets, RFC4 expression was significantly elevated in CC tissues compared to that in normal tissues. Survival analysis based on TCGA and GEO datasets showed that CC patients with high RFC4 expression had a better prognosis than those with low expression. RFC4 expression was strongly correlated with some immunostimulators and immunoinhibitors. RFC4 expression was significantly negatively correlated with activated mast cell immune infiltration, activated CD4 memory T cells, M0 macrophages, and resting natural killer (NK) cells and significantly positively associated with activated dendritic cells, resting dendritic cells, and plasma cells.</p><p><strong>Conclusion: </strong>RFC4 is highly expressed in CC tissues. However, patients with high RFC4 expression in CC have a better prognosis, possibly because RFC4 exerts antitumor effects by affecting the immunostimulatory tumor microenvironment, such as immunostimulatory and dendritic cell infiltration.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1514383"},"PeriodicalIF":2.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208416","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 landscape of hypertrophic cardiomyopathy in Hong Kong Chinese population.","authors":"Derek P H Lee, Ye Cao, Lilei Zhang","doi":"10.3389/fgene.2025.1583838","DOIUrl":"10.3389/fgene.2025.1583838","url":null,"abstract":"<p><strong>Introduction: </strong>Asian populations are underrepresented in the hypertrophic cardiomyopathy (HCM) genomic databases, which are currently largely dominated by Caucasian population. We aim to characterize the genetic landscape of HCM in patients from Hong Kong Chinese population.</p><p><strong>Methods: </strong>From March 2023 to March 2024, fifty-three unrelated patients with an unequivocal clinical diagnosis of HCM were enrolled at a single tertiary center in Hong Kong and underwent genetic testing using a standardized 19-gene panel.</p><p><strong>Results: </strong>In this cohort study, we identified 13 patients (24.5%) with a predominant pathogenic or likely pathogenic (P/LP) variant and 12 patients (22.6%) with a predominant variant of unknown significance (VUS). Most of the P/LP variants identified were in <i>MYBPC3</i> (46.2%, n = 6) or <i>MYH7</i> (38.5%, n = 5). Novel genetic variants were identified in 5 patients. Multiple genetic variants identified in the same patient were common (13.2%, n = 7). All disease-causing variants are rare with allele frequencies <0.00005 in all populations and <0.0002 in East Asian subpopulation. Specifically in this unrelated cohort, we identified several recurrent variants including <i>MYH7</i>:c.1987C>T (p.Arg663Cys) pathogenic missense variant (n = 2), <i>MYBPC3</i>:c.1038_1042dup (p.Met348Thrfs*4) pathogenic truncating variant (n = 3) and <i>MYBPC3</i>:c.1000G>A (p.Glu334Lys) missense VUS (n = 3). Patients with P/LP variants were associated with an increased risk of developing left ventricular dysfunction (p = 0.012).</p><p><strong>Conclusion: </strong>Our study provided insight into the genetic landscape of HCM in Hong Kong Chinese population. We identified several recurrent variants and novel variants in our HCM cohort. Patients with P/LP variants were associated with an increased risk of developing left ventricular dysfunction. Future studies on the potential founder effects of these recurrent variants, cumulative effects of multiple variants, and longitudinal follow up of HCM patients would be useful.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1583838"},"PeriodicalIF":2.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198928","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}