BMC Medical Genomics最新文献

{"title":"Causal association between non-steroidal anti-inflammatory drugs use and the risk of benign prostatic hyperplasia: a univariable and multivariable Mendelian randomization study.","authors":"Zi-He Peng, Ming-Rui Li, Min-Xin He, Jing Liu, Jia-Hao Dou, Ya-Wen Wang, Yao Dong, Chong Yan, Zi-Hao Li, Tie Chong, Zhao-Lun Li","doi":"10.1186/s12920-025-02128-1","DOIUrl":"https://doi.org/10.1186/s12920-025-02128-1","url":null,"abstract":"<p><strong>Background: </strong>The results of earlier observational research on the relationships between the usage of non-steroidal anti-inflammatory medicines (NSAIDs) and the risk of benign prostatic hyperplasia (BPH) have been inconsistent.</p><p><strong>Methods: </strong>To assess these associations, we performed both univariable and multivariable Mendelian randomization (MR) studies. Instrumental variables (IVs) associated with exposures at the significance level (p < 5 × 10^-6) were selected from a comprehensive meta-analysis conducted by the United Kingdom Biobank (UKB). Summary data for BPH were obtained from the FinnGen consortium, which comprised 30,066 cases and 119,297 controls. Sensitivity analyses were performed to evaluate heterogeneity and pleiotropy.</p><p><strong>Results: </strong>We found evidence by univariable MR (UVMR) that genetically predicted NSAIDs use increased the risk of BPH (odds ratio [OR] per unit increase in log odds NSAIDs use: 1.164, 95% confidence interval [CI]: 1.041-1.302, p = 0.008). After controlling for inflammation in multivariable MR (MVMR), the link persisted (OR: 1.165, 95% CI: 1.049-1.293, p = 0.004). There were no indications of potential heterogeneity and pleiotropy in UVMR and MVMR analyses.</p><p><strong>Conclusion: </strong>The results of the MR estimates suggest that genetically predicted NSAIDs use may elevate the risk of BPH. This outcome prompts the imperative for deeper exploration into potential underlying mechanisms.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"60"},"PeriodicalIF":2.1,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750427","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}

{"title":"Whole-genome sequencing, as a powerful diagnostic tool in hearing loss, reveals novel variants in PTPRQ missed by whole-exome sequencing.","authors":"Daniel Bengl, Asuman Koparir, Wahyu Eka Prastyo, Christian Remmele, Marcus Dittrich, Sophie Flandin, Waafa Shehata-Dieler, Clemens Grimm, Thomas Haaf, Michaela A H Hofrichter","doi":"10.1186/s12920-025-02122-7","DOIUrl":"https://doi.org/10.1186/s12920-025-02122-7","url":null,"abstract":"<p><strong>Background/objectives: </strong>Hearing loss (HL) is one of the most common congenital disorders, affecting 1-2 in 1,000 newborns. Modern genetic diagnostics using large gene panels and/or whole exome analysis (WES) can identify disease-causing mutations in 25-50 % of patients, with higher solve rates in individuals with earlier onset.</p><p><strong>Results: </strong>Here, we used whole-genome sequencing (WGS) to reanalyze 14 index patients/families who remained without genetic diagnosis by WES. We were able to identify the genetic cause of HL in 6 families ( <math><mo>∼</mo></math> 43 %). Two families were diagnosed with DFNB84A caused by compound heterozygous recessive mutations in PTPRQ. Three of the four underlying variants, including a structural variant, a deep intronic variant, and a splice variant, escaped detection by WES. Minigene assays confirmed the pathogenicity of the intronic and the splice variants. In addition, we used protein 3D structure prediction and rigid ligand docking to study the pathogenicity of variants that escape nonsense-mediated decay.</p><p><strong>Conclusion: </strong>In our study, we present four novel variants in PTPRQ, three of which were detected only by WGS. To our knowledge, we report here the first pathogenic deep intronic PTPRQ variant causing HL. Our results suggest that the mutational spectrum of PTPRQ is not well covered by standard WES and that PTPRQ-associated hearing loss may be more frequent than previously thought. WGS provides an additional layer of information in the diagnostics of HL.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"59"},"PeriodicalIF":2.1,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750813","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}

{"title":"Severe traumatic brain injury and risk for osteoporosis: a Mendelian randomization study.","authors":"Guoqiang Wang, Jiachen Wang, Dinglong Yang, Lin Liu, Peng Xu","doi":"10.1186/s12920-025-02127-2","DOIUrl":"https://doi.org/10.1186/s12920-025-02127-2","url":null,"abstract":"<p><strong>Background: </strong>The influence of nervous system activity on bone remodeling has been widely reported. Patients with traumatic brain injury (TBI) exhibit a high incidence of osteoporosis (OP). Nevertheless, the relationship between severe TBI (sTBI) and OP remains unclear. We performed Mendelian randomization (MR) analysis to assess the potential causal relationship between sTBI and OP.</p><p><strong>Methods: </strong>Data on exposure and outcomes were acquired from genome-wide association studies (GWAS). Data on OP was obtained from UK Biobank (5,266 cases of OP and 331,893 controls). Data on sTBI was obtained from FinnGen Consortium (6,687 cases and 370,590 controls). Single nucleotide polymorphisms (SNPs) that underwent strict screening were regarded as instrumental variables. We used the inverse variance weighted (IVW), constrained maximum likelihood and model averaging (CML-MA), MR-Egger, and weighted median methods for causal effect estimation. To test the reliability of the results, sensitivity analysis was performed using Cochran's Q, leave-one-out, MR-Egger intercept, and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) tests.</p><p><strong>Results: </strong>The IVW analysis indicates that sTBI and OP have a suggestive association (odds ratio [OR] = 1.004, 95% confidence interval [CI] = 1.001,1.007; p = 0.002), and no heterogeneity (Q = 11.536, p = 0.241) or directional pleiotropy was observed (egger_intercept = 7.368 × 10^- 5, p = 0.870). The robustness of the results was validated using a leave-one-out sensitivity test.</p><p><strong>Conclusion: </strong>According to the MR analysis, sTBI and OP are likely suggestively related. This finding contributes to the prevention of OP in patients with sTBI and provides genetic evidence supporting the theory that the nervous system regulates bone remodeling.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"61"},"PeriodicalIF":2.1,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750505","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}

{"title":"N6-methyladenine identification using deep learning and discriminative feature integration.","authors":"Salman Khan, Islam Uddin, Sumaiya Noor, Salman A AlQahtani, Nijad Ahmad","doi":"10.1186/s12920-025-02131-6","DOIUrl":"https://doi.org/10.1186/s12920-025-02131-6","url":null,"abstract":"<p><p>N6-methyladenine (6 mA) is a pivotal DNA modification that plays a crucial role in epigenetic regulation, gene expression, and various biological processes. With advancements in sequencing technologies and computational biology, there is an increasing focus on developing accurate methods for 6 mA site identification to enhance early detection and understand its biological significance. Despite the rapid progress of machine learning in bioinformatics, accurately detecting 6 mA sites remains a challenge due to the limited generalizability and efficiency of existing approaches. In this study, we present Deep-N6mA, a novel Deep Neural Network (DNN) model incorporating optimal hybrid features for precise 6 mA site identification. The proposed framework captures complex patterns from DNA sequences through a comprehensive feature extraction process, leveraging k-mer, Dinucleotide-based Cross Covariance (DCC), Trinucleotide-based Auto Covariance (TAC), Pseudo Single Nucleotide Composition (PseSNC), Pseudo Dinucleotide Composition (PseDNC), and Pseudo Trinucleotide Composition (PseTNC). To optimize computational efficiency and eliminate irrelevant or noisy features, an unsupervised Principal Component Analysis (PCA) algorithm is employed, ensuring the selection of the most informative features. A multilayer DNN serves as the classification algorithm to identify N6-methyladenine sites accurately. The robustness and generalizability of Deep-N6mA were rigorously validated using fivefold cross-validation on two benchmark datasets. Experimental results reveal that Deep-N6mA achieves an average accuracy of 97.70% on the F. vesca dataset and 95.75% on the R. chinensis dataset, outperforming existing methods by 4.12% and 4.55%, respectively. These findings underscore the effectiveness of Deep-N6mA as a reliable tool for early 6 mA site detection, contributing to epigenetic research and advancing the field of computational biology.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"58"},"PeriodicalIF":2.1,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742103","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}

{"title":"Exploring diagnostic m6A regulators in primary open-angle glaucoma: insight from gene signature and possible mechanisms by which key genes function.","authors":"Xinyue Zhang, Jiawei Chen, Xiaoyu Zhou, Dengming Zhou, Li Liao, Yang Zhao, Ping Wu, Fen Nie, Zhimin Liao, Ziyan Cai, Xuanchu Duan","doi":"10.1186/s12920-025-02123-6","DOIUrl":"10.1186/s12920-025-02123-6","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to interrogate the potential role of N6-methyladenosine (m6A) regulators in the process of trabecular meshwork (TM) tissue damage in patients with primary open-angle glaucoma (POAG).</p><p><strong>Methods: </strong>Firstly, the expression profile of m6A regulators in TM tissues of POAG patients was comprehensively analyzed by bioinformatics analysis; Plasmid transfection and siRNA gene interference were used to enhance or weaken the expression levels of YTHDC2 in human trabecular meshwork cells (HTMCs); Cell migration ability was detected by transwell chamber assay; Immunofluorescence staining assay was used to evaluate the expression of extracellular matrix (ECM) related proteins.</p><p><strong>Results: </strong>Through the analysis of GSE27276 database, 5 m6A regulators with different expression in POAG were screened out. The results of random forest model showed that these 5 m6A regulators exhibited diagnostic potential and were characteristic genes of POAG. All POAG samples could be effectively divided into two groups based on the expression levels of these 5 hub m6A regulators. Immune cell infiltration analysis indicated that the levels of activated CD8⁺ T cells and regulatory T cells were different in the two subtypes. HTMC oxidative stress cell model and TGF-β2 stimulation cell model were further constructed to verify the expression of the aforementioned hub m6A regulators, and it was found that YTHDC2 mRNA showed the same expression trend in both models. The silencing of YTHDC2 enhanced the migration ability of HTMCs and increased the synthesis ability of ECM. However, when YTHDC2^ΔYTH, which lacks the YTH domain, is overexpressed in HTMCs, there is no significant change in the ECM synthesis ability.</p><p><strong>Conclusions: </strong>The differentially expressed m6A regulators in TM tissues may serve as potential diagnostic biomarkers for POAG. And, in HTMCs, the expression level of YTHDC2 mRNA was changed under oxidative stress or TGF-β2 intervention, and then exerted its regulation on cell migration and ECM synthesis capability through m6A modification, which may be an important part of the disease process of POAG.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"57"},"PeriodicalIF":2.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive integration of data on the association of ITPKC polymorphisms with susceptibility to Kawasaki disease: a meta-analysis.","authors":"Atefeh Habibi, Hanieh Talebi, Reza Bahrami, Mohammad Golshan-Tafti, Amirhossein Shahbazi, Seyed Alireza Dastgheib, Azadeh Tahooni, Maryam Vafapour, Heewa Rashnavadi, Melina Pourkazemi, Maryam Yeganegi, Elnaz Sheikhpour, Hossein Neamatzadeh","doi":"10.1186/s12920-025-02121-8","DOIUrl":"10.1186/s12920-025-02121-8","url":null,"abstract":"<p><strong>Background: </strong>This study aims to conduct a comprehensive meta-analysis of existing research to define clear associations between variations in the ITPKC gene and the risk of developing Kawasaki disease (KD).</p><p><strong>Methods: </strong>A comprehensive search was conducted across multiple databases, including but not limited to PubMed, Scopus, EMBASE, and CNKI, up to June 1, 2024, to gather relevant information. This search utilized keywords and MeSH terms related to hyperbilirubinemia and genetic factors. The inclusion criteria encompassed original case-control, longitudinal, or cohort studies. Correlations were analyzed as odds ratios (ORs) with 95% confidence intervals (CIs) using Comprehensive Meta-Analysis software.</p><p><strong>Results: </strong>Eighteen case-control studies with 5,434 KD cases and 9,419 controls were analyzed. Of these, ten studies assessed 3,129 KD cases and 6,172 controls for the rs28493229 variant, four examined 1,039 cases and 1,688 controls for the rs2290692 variant, two focused on 595 cases and 820 controls for the rs7251246 variant, and two investigated 671 cases and 739 controls for the rs10420685 variant. Results showed a significant association between the rs28493229 polymorphism and increased KD risk across all five genetic models. Subgroup analysis indicated this polymorphism correlates with KD susceptibility in Asians but not in the Chinese population. In contrast, no associations were found between the rs2290692, rs7251246, and rs10420685 polymorphisms and KD risk.</p><p><strong>Conclusions: </strong>Our pooled data indicate a significant association between the ITPKC rs28493229 polymorphism's minor allele and an increased risk of developing KD, suggesting this variant may enhance susceptibility. Conversely, SNPs rs2290692, rs7251246, and rs10420685 do not demonstrate a statistically significant relationship with KD.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"56"},"PeriodicalIF":2.1,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the mechanism of BGN in progression and metastasis of ccRCC.","authors":"Hanqing Xia, Tianzhen He, Xueyu Li, Kai Zhao, Zongliang Zhang, Guanqun Zhu, Han Yang, Xuechuan Yan, Qinglei Wang, Zhaofeng Li, Zaiqing Jiang, Ke Wang, Xinbao Yin","doi":"10.1186/s12920-025-02124-5","DOIUrl":"10.1186/s12920-025-02124-5","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the role of Biglycan(BGN) in the progression and metastasis of clear cell renal cell carcinoma(ccRCC).</p><p><strong>Methods: </strong>Based on multiple public databases, we investigated the expression level of BGN in ccRCC, its clinical significance, and its association with immune cells. Real-time fluorescence quantitative polymerase chain reaction(PCR) was employed to validate BGN expression in tumor and adjacent normal tissues from ten patients. We utilized RNA sequencing results for further analysis, including differential gene analysis, GO-KEGG analysis, and GSEA analysis, to identify the signaling pathways through which BGN exerts its effects. BGN knockdown cells(786-0 and Caki-1) were generated through lentiviral transfection to examine the impact of BGN on ccRCC. Cell proliferation, migration, and invasion were assessed using CCK8, colony formation, wound healing, Transwell migration, and invasion assays, respectively.</p><p><strong>Results: </strong>Our findings from database analysis and PCR revealed a significant upregulation of BGN expression in kidney cancer tissues compared to normal tissues. Further analysis demonstrated a correlation between high BGN expression and ccRCC progression and immune infiltration. In vitro experiments confirmed that BGN silencing effectively inhibited cell proliferation, migration, and invasion of ccRCC. Mechanistically, these effects may be mediated through the MAPK signaling pathway.</p><p><strong>Conclusion: </strong>BGN potentially plays a pivotal role in the progression and metastasis of ccRCC, possibly acting through the MAPK signaling pathway. Therefore, BGN holds promise as a potential therapeutic target for ccRCC.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"55"},"PeriodicalIF":2.1,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unravelling the transcriptomic characteristics of bronchoalveolar lavage in post-covid pulmonary fibrosis.","authors":"Mohammad Shadab Ali, Vijay Hadda, Sonia Verma, Anita Chopra, Saurabh Mittal, Karan Madan, Pawan Tiwari, Tejas Menon Suri, Anant Mohan","doi":"10.1186/s12920-025-02110-x","DOIUrl":"10.1186/s12920-025-02110-x","url":null,"abstract":"<p><strong>Background: </strong>Post-Covid Pulmonary Fibrosis (PCPF) has emerged as a significant global issue associated with a poor quality of life and significant morbidity. Currently, our understanding of the molecular pathways of PCPF is limited. Hence, in this study, we performed whole transcriptome sequencing of the RNA isolated from the bronchoalveolar lavage (BAL) samples of PCPF and compared it with idiopathic pulmonary fibrosis (IPF) and non-ILD (Interstitial Lung Disease) control to understand the gene expression profile and associated pathways.</p><p><strong>Methods: </strong>BAL samples from PCPF (n = 3), IPF (n = 3), and non-ILD Control (n = 3) (individuals with apparent healthy lung without interstitial lung disease) groups were obtained and RNA were isolated for whole transcriptomic sequencing. Differentially Expressed Genes (DEGs) were determined followed by functional enrichment analysis and qPCR validation.</p><p><strong>Results: </strong>A panel of differentially expressed genes were identified in bronchoalveolar lavage fluid cells (BALF) of PCPF as compare to control and IPF. Our analysis revealed dysregulated pathways associated with cell cycle regulation, immune responses, and neuroinflammatory processes. Real-time validation further supported these findings. The PPI network and module analysis shed light on potential biomarkers and underscore the complex interplay of molecular mechanisms in PCPF. The comparison of PCPF and IPF identified a significant downregulation of pathways that were more prominent in IPF.</p><p><strong>Conclusion: </strong>This investigation provides crucial insights into the molecular mechanism of PCPF and also outlines avenues for prospective research and the development of therapeutic approaches.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"54"},"PeriodicalIF":2.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11917041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatics identification and validation of pyroptosis-related gene for ischemic stroke.","authors":"Xinying Shang, Rui Wei, Di Yang, Bawei Yu, Wei Zhang","doi":"10.1186/s12920-025-02119-2","DOIUrl":"10.1186/s12920-025-02119-2","url":null,"abstract":"<p><strong>Background: </strong>Ischemic stroke (IS) is one of the common and frequent diseases with extremely high lethality and disability in the world, and there is no effective treatment at present. This study aimed to screen hub genes involved in cerebral ischemia/reperfusion injury (CIRI) and pyroptosis, and explore promising intervention targets.</p><p><strong>Methods: </strong>CIRI-related genes (GSE202659 and GSE131193) and pyroptosis-related genes (PRGs) in mice were obtained from the Gene Expression Omnibus (GEO) and GeneCards database. We screened for LASSO regression to construct a prognostic model of GSE131193 and PRGs and examined by GSE137482. The functional enrichment analysis of Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were performed on pyroptosis-related differentially expressed genes (PRDEGs) of GSE202659.The key modules for CIRI and pyroptosis were identified by Weight Gene Co-expression Network Analysis (WGCNA). Subsequently, Protein-protein Interaction (PPI) network and the Cytoscape was constructed to screen out hub genes. Used the starBase to predict miRNA interacting with hub genes and constructed mRNA-miRNA-lncRNA interaction networks. CIRI-related Molecular Subtypes were constructed for hub genes. The relationship between immune cells and hub genes was verified via CIBERSORT. Finally, we selected C57BL/6 mice to construct models to confirm hub genes by enzyme linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (RT-PCR), western blot, and Immunofluorescence.</p><p><strong>Results: </strong>A total of 272 PRGs and 35 PRDEGs were screened. An eight-gene risk prediction models were established (AUC = 0.868). GO, KEGG, GSEA and GSVA analyses revealed that PRDEGs were mainly involved in positive regulation of cytokine production, and NOD-like receptor signaling pathway. And then, seven hub genes (Irf1, Icam1, Tlr2, Tnf, Cebpb, Il1rn, and Casp8) were identified by PPI. Icam1, Tnf, Cebpb, Il1rn, and Casp8 had high expression profiles in Cluster2 by hierarchical clustering. The immune infiltration analysis results showed that among the hub genes, Cebpb, Il1rn, and Casp8, showed a significant positive correlation with the degree of NK.Actived, and Icam1 showed a significant negative correlation with B.Cells.Memory. The results of animal experiments significantly demonstrated an upregulation of Irf1, Icam1, Tlr2, Cebpb, and Il1rn.</p><p><strong>Conclusion: </strong>Our finding indicated that Irf1, Icam1, Tlr2, Cebpb, and Il1rn are hub genes associated with pyroptosis, and these genes are all associated with different immune cells, so as to provide new targets for the prevention and treatment of IS from the perspective of pyroptosis.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"53"},"PeriodicalIF":2.1,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inherited rare epidermal growth factor receptor mutation and somatic mutations in patients with non-small cell lung cancer: a case report.","authors":"Zacharenia Saridaki, Elena Fountzilas, Athanasios Alexopoulos, Niki Karachaliou","doi":"10.1186/s12920-025-02113-8","DOIUrl":"10.1186/s12920-025-02113-8","url":null,"abstract":"<p><strong>Background: </strong>Recent advances in molecular oncology have increasingly illuminated the role of germline EGFR mutations in non-small cell lung cancer (NSCLC). This case report presents the presence of a unique familial occurrence of EGFR mutations in patients with NSCLC.</p><p><strong>Case description: </strong>A mother and son, both never-smokers of Caucasian ethnicity, were diagnosed with advanced metastatic lung adenocarcinoma. In one patient, tumor molecular analysis by next generation sequencing (NGS) identified two EGFR mutations: the activating mutation c.2573T > G; p.Leu858Arg (p.L858R) in exon 21 of the EGFR gene, and the somatic non-pathogenic mutation c.2612 C > A; p.Ala871Glu (p.A871E) in exon 21 of the EGFR gene. The second patient also harbored the same two EGFR mutations. The patient underwent genetic testing which revealed the germline origin of the A871E mutation. Whether the presence of this mutations was associated with increased predisposition to cancer has yet to be determined. Our case report highlights the need for further exploration of the role of germline mutations, including the A871E mutation, in tumorigenesis and its implications for treatment response and inheritance patterns.</p><p><strong>Conclusions: </strong>The investigation and comprehension of the significance of each individual EGFR mutation hold the promise for potential in cancer prevention or early diagnosis within family cohorts and understanding the mechanisms of tumorigenesis in sporadic cases.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"51"},"PeriodicalIF":2.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}