BMC Medical Genomics最新文献

{"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}

{"title":"Genomic characteristics and prognostic correlations in Chinese multiple myeloma patients.","authors":"Xi Chen, Tianchen Luo, Wenhui Zhang, Sheng Wang, Mengxuan Zhu, Haiyan He, Jin Liu, Jing Lu, Wanting Qiang, Yanchun Jia, Nan Hou, Xuenan Zhao, Shan Zhang, Jing Li, Juan Du","doi":"10.1186/s12920-025-02116-5","DOIUrl":"10.1186/s12920-025-02116-5","url":null,"abstract":"<p><strong>Background: </strong>Multiple myeloma (MM) is a hematologic malignancy characterized by the proliferation of abnormal clonal plasma cells in the bone marrow. The heterogeneity in Chinese MM populations remains underexplored.</p><p><strong>Methods: </strong>We conducted whole-exome sequencing (WES) on 241 tumor samples, complemented by RNA sequencing (RNA-seq) on 131 samples from 212 Chinese MM patients.</p><p><strong>Results: </strong>We identified a novel mutational signature and analyzed molecular differences between newly diagnosed MM (NDMM) and relapsed/refractory MM (RRMM) patients. NFKBIA mutations were notably more frequent in NDMM patients compared to the MMRF-COMMPASS cohort (4/50 vs 22/937, p = 0.048), with additional recurrent mutations in several genes like TTN, IGLL5 and SYNE1. In RRMM patients, UBR5 mutations were more prevalent (4/24 vs 0/50, p = 0.01), alongside frequent mutations in OBSCN, CACNA1H, and HSPG2. Clonal evolution was assessed through multiple time points and locations, identifying genes potentially linked to circulating plasma cell formation. Cox regression analysis revealed that age and mutations in OBSCN and RB1 were significant predictors of progression-free survival (PFS) in NDMM patients. Additionally, albumin, β2-microglobulin, and RB1 mutations were correlated with overall survival (OS).</p><p><strong>Conclusions: </strong>In summary, we characterized the genomic landscape of MM in diverse Chinese populations, confirmed clonal evolution, and identified prognostic genes.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"50"},"PeriodicalIF":2.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633393","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":"Comprehensive clinical and genetic characterization of hyperprogressive biliary tract cancer during PD-1 blockade monotherapy: case report and literature review.","authors":"Kang-Xin Wang, Xu-Dong Yang, Fen Guo, Hui Sun, Yue-Yu Fang, Nan-Yuan Jiang, Xiao-Feng Chen","doi":"10.1186/s12920-025-02097-5","DOIUrl":"10.1186/s12920-025-02097-5","url":null,"abstract":"<p><strong>Background: </strong>Some genetically characterized patients show the rapid disease progression during immune checkpoint inhibitors (ICIs) monotherapy, a phenomenon known as hyperprogressive disease (HPD).</p><p><strong>Case presentation: </strong>Herein we report a relevant case of biliary tract cancer (BTC) that initially responded to gemcitabine plus oxaliplatin (GEMOX) and PD-1 blockade but subsequently developed HPD in the process of PD-1 blockade maintenance therapy, leading to death within two weeks. Genomic analysis revealed mutations in CDKN2A, PIK3CA, KRAS and EPHA2 in both baseline and hyperprogressive plasma and tumor samples. Notably, higher KRAS mutation abundance was observed in plasma and ascites after disease progression.</p><p><strong>Conclusions: </strong>These findings suggest a potential association between these negative genes especially KRAS mutation and HPD. Therefore, administration of PD-1 blockade monotherapy in this subgroup of patients harboring KRAS mutation should be performed with caution. Further studies are warranted to confirm these results and explore the correlation between genomic mutations and HPD.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"52"},"PeriodicalIF":2.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633390","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":"Spectrum of genetic variants associated with maple syrup urine disease in the Middle East, North Africa, and Türkiye (MENAT): a systematic review.","authors":"Salma Younes, Razan Elkahlout, Houda Kilani, Sarah Okashah, Hussain Al Sharshani, Zoulikha Rezoug, Hatem Zayed, Nader Al-Dewik","doi":"10.1186/s12920-025-02083-x","DOIUrl":"10.1186/s12920-025-02083-x","url":null,"abstract":"<p><strong>Background: </strong>Maple syrup urine disease (MSUD) is a hereditary metabolic disorder caused by a deficiency in the branched-chain α-keto acid dehydrogenase (BCKD) enzymatic complex. The Middle East and North Africa, and Türkiye (MENAT) region has witnessed a significant rise in the prevalence of MSUD due to high rates of consanguinity. Despite numerous genetic association studies, the complex relationships between genotype and phenotype in MSUD remain elusive.</p><p><strong>Aim: </strong>This study aimed to systematically review the variants significantly associated with MSUD in the MENAT region.</p><p><strong>Methods: </strong>We systematically searched four literature databases (PubMed, Scopus, Web of Science, and Science Direct) from inception until December 2023 to gather all reported genetic data pertaining to MSUD in the MENAT region. Quality assessment and data extraction were diligently performed by a team of six investigators.</p><p><strong>Results: </strong>A total of 16 studies, involving patients, were included in this systematic review. Among them, 211 patients presented with 105 variants located within genes known to be associated with MSUD. The majority of the identified MSUD variants were found in BCKDHA (38%), followed by BCKDHB (38%), DBT (23%), and PPM1K (1%). Notably, 77% of the captured variants were unique to the MENAT region.</p><p><strong>Conclusion: </strong>Our systematic review reveals a distinctive genetic and clinical susceptibility profile of MSUD among individuals from the MENAT region. These findings highlight the importance of understanding the specific genetic landscape of MSUD in this population. Further research is warranted to elucidate the complex genotype-phenotype relationships in MSUD in the MENAT region.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"49"},"PeriodicalIF":2.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623367","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}