{"title":"Association of MSH2, MSH6, and MLH1 polymorphisms with susceptibility and survival in lung cancer patients.","authors":"Jing Cheng, Chao Zuo, Dongli Yang, Yi Liu, Yu Wang, Yongchao Qiao","doi":"10.1007/s13258-025-01681-4","DOIUrl":"https://doi.org/10.1007/s13258-025-01681-4","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer (LC) is the leading cause of cancer-related deaths globally. Genetic variants in mismatch repair (MMR) genes, such as MutS homolog 2 (MSH2), MutS homolog 6 (MSH6) and MutL homolog 1 (MLH1), may influence individual susceptibility and clinical outcomes in LC.</p><p><strong>Objective: </strong>This study investigated the associations of genetic polymorphisms in MSH2, MSH6, and MLH1 with susceptibility and survival outcomes in lung cancer patients in the Guangxi Zhuang population.</p><p><strong>Methods: </strong>This study included a cohort of 192 LC patients and 262 healthy controls. The association of MSH2, MSH6, and MLH1 polymorphisms with susceptibility to small cell lung cancer (SCLC), lung adenocarcinoma (LUAD), and lung squamous carcinoma (LUSC) was evaluated using case-control methods, and protein expression differences were analysed by immunohistochemistry. The genotypes of genetic variations were detected using high-throughput SNP-scan technology. The Kaplan-Meier survival curve and log-rank test were used to assess the influence of individual genetic variants on prognostic outcomes in lung cancer patients.</p><p><strong>Results: </strong>Multivariate logistic regression identified significant associations of rs2303428 and rs1042821 with increased lung cancer risk, especially in SCLC and LUSC. The GA and GG genotypes of rs1042821 were linked to higher SCLC risk (OR = 4.415 and 2.685; P = 0.019), the TC genotype of rs2303428 was associated with elevated LUSC risk (OR = 3.993; P = 0.034). No associations were found for rs1800734 or in LUAD. Immunohistochemistry showed increased MSH2 and MSH6 expression in risk genotypes, with no genotype-related changes in MLH1. In LUAD, the CC genotype of rs2300789 was associated with poorer overall survival compared to TC (P = 0.047), with no significant differences in other comparisons.</p><p><strong>Conclusion: </strong>rs2303428 and rs1042821 polymorphisms were associated with increased lung cancer susceptibility and altered protein expression. Additionally, the CC genotype of rs2300789 was linked to poorer overall survival in LUAD.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genes & genomicsPub Date : 2025-09-04DOI: 10.1007/s13258-025-01677-0
Il-San Jeong, Jee-Woo Seo, Seung-Jin Park, Seon-Young Kim, Seon-Kyu Kim, Seung-Woo Baek
{"title":"Deep learning-driven whole-slide image analysis predicts chemo-resistance and motility subtypes in muscle-invasive bladder cancer.","authors":"Il-San Jeong, Jee-Woo Seo, Seung-Jin Park, Seon-Young Kim, Seon-Kyu Kim, Seung-Woo Baek","doi":"10.1007/s13258-025-01677-0","DOIUrl":"10.1007/s13258-025-01677-0","url":null,"abstract":"<p><strong>Background: </strong>Muscle-invasive bladder cancer (MIBC) is a clinically aggressive and heterogeneous disease with variable treatment responses. Transcriptome-based classifications, such as the Chemoresistance-Motility (CrM) signature, are valuable for understanding therapeutic resistance, but their clinical use is often hindered by high cost and tissue requirements. This study explores an alternative, scalable approach using deep learning analysis of whole slide images (WSIs).</p><p><strong>Objective: </strong>We aimed to evaluate whether patch-level predictions from deep learning models applied to WSIs can accurately predict transcriptome-derived CrM subtypes and reflect tumor microenvironment (TME) characteristics in MIBC.</p><p><strong>Methods: </strong>We analyzed 192 WSIs from 152 TCGA-BLCA patients. A pretrained deep learning model (densenet169-kather100k) was used to classify eight distinct tissue types per patch. A key histological metric, the SAM-to-DNT ratio, which represents the ratio of stromal, adipose, and smooth muscle (SAM) tissue types to debris, normal, and tumor epithelium (DNT) tissue types, was derived from these proportions. A random forest model was then trained on these features to predict CrM subtypes.</p><p><strong>Results: </strong>The WSI-derived SAM-to-DNT ratio showed a strong positive correlation with the CrM score (R = 0.453) and transcriptome-based TME scores, such as cancer-associated fibroblasts (R = 0.398). Our random forest model successfully classified CrM subtypes with a balanced accuracy of 0.75, outperforming other algorithms. Feature importance analysis identified adipose tissue (ADI) and tumor epithelium (TUM) as the most predictive features for CrM status.</p><p><strong>Conclusions: </strong>Deep learning analysis of routine histological WSIs can serve as a practical, low-cost surrogate for molecular profiling, effectively capturing transcriptomic subtypes associated with chemoresistance in MIBC. This approach provides a viable method for patient stratification and establishes a foundation for future multi-modal precision oncology applications.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genes & genomicsPub Date : 2025-09-01Epub Date: 2025-08-12DOI: 10.1007/s13258-025-01659-2
Kwan Sik Park, In Sook Jeon, Jin Tae Hong, Bumhee Yang, Joong-Kook Choi
{"title":"Regulation of intracellular proliferation of Salmonella typhimurium by CD63.","authors":"Kwan Sik Park, In Sook Jeon, Jin Tae Hong, Bumhee Yang, Joong-Kook Choi","doi":"10.1007/s13258-025-01659-2","DOIUrl":"10.1007/s13258-025-01659-2","url":null,"abstract":"<p><strong>Background: </strong>Autophagy is an intracellular degradation process involving the lysosomal breakdown of unnecessary or abnormal cellular components. Targets of autophagy include pathogens, altered organelles, and protein aggregates, which are sequestered within double-membrane-limited vesicles known as autophagosomes. A variety of lysosomal membrane proteins play essential roles in numerous cellular processes, including lysosomal acidification, metabolite transport, and interaction with other membrane systems. Cluster of differentiation 63 (CD63), a member of the transmembrane 4 superfamily, is present on the cell surface and in intracellular membrane compartments, such as endosomal and lysosomal membranes. This protein is also associated with several diseases, including Hermansky-Pudlak syndrome and immunoglobulin E-mediated allergies. However, its role in the autophagy pathway and intracellular bacterial proliferation remains poorly understood.</p><p><strong>Objective: </strong>This study aimed to investigate changes in CD63 expression in response to Salmonella infection and to analyze the effects of these changes on Salmonella proliferation.</p><p><strong>Methods: </strong>Changes in CD63 expression were examined following Salmonella infection using cellular models. Expression regulation was assessed for dependence on nuclear factor kappa B signaling. Colocalization of CD63 was evaluated with green fluorescent protein-tagged Salmonella and the lysosomal marker LysoTracker. Intracellular Salmonella titers were measured and correlated with CD63 expression levels to determine impacts on bacterial survival.</p><p><strong>Results: </strong>CD63 expression increased in response to Salmonella infection in a nuclear factor kappa B-dependent manner. CD63 colocalized with green fluorescent protein-tagged Salmonella and the lysosomal marker LysoTracker. The titer of intracellular Salmonella was inversely correlated with CD63 expression, suggesting that higher CD63 levels reduce bacterial survival.</p><p><strong>Conclusion: </strong>CD63 contributes to the regulation of intracellular Salmonella survival through the autophagy pathway, specifically xenophagy (autophagy targeting pathogens). This is the first report documenting the inhibition of Salmonella proliferation via induction of CD63 expression and Xenophagy.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"973-982"},"PeriodicalIF":1.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144821272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genes & genomicsPub Date : 2025-09-01Epub Date: 2025-07-24DOI: 10.1007/s13258-025-01662-7
Yoonha Ju, Rajendran Sathishraj, Bikram S Gill, Dal-Hoe Koo
{"title":"Aneusomaty in glyphosate-resistant Amaranthus palmeri and its hybrid with Amaranthus tuberculatus.","authors":"Yoonha Ju, Rajendran Sathishraj, Bikram S Gill, Dal-Hoe Koo","doi":"10.1007/s13258-025-01662-7","DOIUrl":"10.1007/s13258-025-01662-7","url":null,"abstract":"<p><strong>Background: </strong>Glyphosate [N-(phosphonomethyl) Glycine], commonly known as Roundup, is one of the most widely used herbicides for controlling crop weeds. However, its extensive use has led to the rapid evolution of glyphosate-resistant (GR) weed populations, often via amplification of the target gene EPSPS (5-enolpyruvylshikimate-3-phosphate synthase), sometimes accompanied by chromosomal abnormalities.</p><p><strong>Objective: </strong>This study investigates the occurrence and characteristics of aneusomaty in GR Amaranthus palmeri and its interspecific hybrids with A. tuberculatus.</p><p><strong>Methods: </strong>Fluorescence in situ hybridization (FISH) was used to cytologically characterize glyphosate resistance and aneusomaty in A. palmeri.</p><p><strong>Results: </strong>Aneusomaty was observed in GR A. palmeri and its hybrids with A. tuberculatus. Root tips from a single GR A. palmeri plant exhibited two distinct chromosome numbers: 2n = 34 and 2n = 68. Similarly, F1 hybrid root tips [A. tuberculatus (2n = 32) x A. palmeri (2n = 34)] displayed 2n = 33 and 2n = 66. The pseudo F<sub>2</sub> plants, apomictically derived from F<sub>1</sub> hybrids, consistently showed 2n = 50 chromosomes. FISH targeting 5 S rDNA loci, was used to distinguish the genomes of A. palmeri and A. tuberculatus in the F<sub>1</sub> and pseudo F<sub>2</sub> plants. The pseudo F<sub>2</sub> plants (2n = 50) contained the diploid chromosome set of A. palmeri (2n = 34) and the haploid chromosome set of A. tuberculatus (n = 16). Notably, these sporadic chromosome duplications occurred only in glyphosate-resistant (GR) plants and were absent in glyphosate-sensitive (GS) plants.</p><p><strong>Conclusion: </strong>Our results suggest that aneusomaty-related increases in chromosome numbers during the sporophytic phase may facilitate EPSPS gene duplication, offering a previously unrecognized mechanism contributing to glyphosate resistance in A. palmeri.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"953-960"},"PeriodicalIF":1.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genes & genomicsPub Date : 2025-09-01Epub Date: 2025-08-04DOI: 10.1007/s13258-025-01661-8
Sunkyung Choi, Kee K Kim
{"title":"Nuclear ribonucleoprotein condensates as platforms for gene expression regulation.","authors":"Sunkyung Choi, Kee K Kim","doi":"10.1007/s13258-025-01661-8","DOIUrl":"10.1007/s13258-025-01661-8","url":null,"abstract":"<p><p>Liquid-liquid phase separation (LLPS) segregates the eukaryotic nucleus into membraneless ribonucleoprotein (RNP) condensates that orchestrate multiple stages of gene expression. In contrast to cytoplasmic granules, these nuclear assemblies lie in direct contact with chromatin and nascent pre‑mRNA, granting first‑order control over transcriptional initiation, co‑transcriptional RNA processing, and mRNA export. Consequently, alterations in their biochemical properties can propagate transcriptome‑wide disturbances and increase disease susceptibility. This review synthesizes current knowledge of the molecular composition, architectural scaffolds, and regulatory roles of the four canonical nuclear condensates-nuclear speckles, paraspeckles, Cajal bodies, and histone locus bodies. We discuss how these dynamic hubs accelerate spliceosome assembly, enforce RNA quality control, and reprogram transcription under stress, and we compile evidence that condensate hardening, mislocalization, or compositional rewiring contributes to diverse pathologies. Finally, we evaluate emerging therapeutic strategies that reengineer condensate phase behavior and outline future directions for biophysical and multi-omics approaches needed to translate condensate biology into precision medicine.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"935-951"},"PeriodicalIF":1.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"NCOA4 inhibits glioma progression by suppressing the Sonic Hedgehog pathway and its overexpression indicates a better glioma prognosis.","authors":"Kaining Liu, Hu Wang, Tian Qiu, Guangxiu Wang, Anling Zhang, Zhifan Jia, Xiaoguang Tong","doi":"10.1007/s13258-025-01666-3","DOIUrl":"10.1007/s13258-025-01666-3","url":null,"abstract":"<p><strong>Background: </strong>Nuclear receptor coactivator 4 (NCOA4) is known to be involved in ferroptosis. However, its expression and function in gliomas are still unclear.</p><p><strong>Objective: </strong>To assess the expression of NCOA4 in gliomas and explore the mechanisms by which NCOA4 affects glioma progression.</p><p><strong>Methods: </strong>RNA-seq data for glioma patient tissues and normal brain tissues were obtained from The Cancer Genome Atlas and the Genotype Tissue Expression project. NCOA4 expression was assessed by Western blotting (WB) and immunohistochemistry (IHC). Overexpression and knockdown of NCOA4 were induced in glioma cell lines via transduction of recombinant adenovirus encoding NCOA4 and NCOA4 siRNA, respectively. Cell Counting Kit-8 (CCK-8), Transwell and flow cytometry assays were performed to assess cell proliferation, invasion and apoptosis.</p><p><strong>Results: </strong>WB and IHC revealed that NCOA4 was markedly downregulated in glioma cell lines and human specimens compared to controls, and high NCOA4 expression was associated with a better glioma prognosis. NCOA4 overexpression inhibited glioma cell growth and invasion and induced apoptosis, whereas NCOA4 knockdown promoted glioma cell growth. PTCH1 was predicted to interact with NCOA4 via bioinformatics analysis. NCOA4 overexpression increased the expression of PTCH1 and suppressed the expression of SMO, Bcl-2 and the nuclear translocation of Gli1, indicating that NCOA4 suppresses the SHH pathway. PTCH1 knockdown reversed the inhibitory effects of NCOA4 on the malignant behaviours of glioma cells.</p><p><strong>Conclusions: </strong>These results suggest that NCOA4 is downregulated in gliomas and that its overexpression predicts better overall survival in glioma patients. Mechanistically, NCOA4 overexpression inhibits the progression of glioma by suppressing the SHH pathway.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"961-972"},"PeriodicalIF":1.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12405388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144821271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genes & genomicsPub Date : 2025-08-18DOI: 10.1007/s13258-025-01665-4
Wenlie Chen, Yuanlu Huang, Li Lei, Rui Zhang, Li Fu, Jinwen Liao, Shaohua Wang, Zhenzhuang Zou
{"title":"Identification of a hypoxia-related gene signature associated with childhood asthma.","authors":"Wenlie Chen, Yuanlu Huang, Li Lei, Rui Zhang, Li Fu, Jinwen Liao, Shaohua Wang, Zhenzhuang Zou","doi":"10.1007/s13258-025-01665-4","DOIUrl":"https://doi.org/10.1007/s13258-025-01665-4","url":null,"abstract":"<p><strong>Background: </strong>Hypoxia is a significant manifestation of severe asthma in children. An early and accurate diagnosis is crucial for enhancing treatment outcomes and mitigating long-term complications. This study aims to utilize bioinformatics analysis to investigate hypoxia-related genes (HRGs) in childhood asthma.</p><p><strong>Objective: </strong>This study aims to develop a diagnostic model and identify key hypoxia-related biomarkers in childhood asthma based on transcriptomic data analysis.</p><p><strong>Methods: </strong>Hypoxia-related differentially expressed genes (HRDEGs) were identified from bronchial epithelial transcriptomes (GSE27011/GSE40732 datasets) using limma analysis. A diagnostic model was developed using LASSO regression, and hub genes were identified via protein-protein interaction (PPI) networks. Asthma subtyping and immune microenvironment characterization were conducted using ConsensusClusterPlus and CIBERSORTx, respectively. Experimental validation in house dust mite (HDM)-induced asthmatic mice confirmed transcriptional changes in candidate genes.</p><p><strong>Results: </strong>We obtained 19 HRDEGs and 11 model genes (AHR, AKR1C3, ELP3, GNAL, GZMB, LPP, MAFG, PDGFD, PPP1R12B, SYNE2, and TAF15). Regression analyses demonstrated the model's robust diagnostic performance. PPI analysis identified 10 hub genes associated with asthma, with AKR1C3 showing high diagnostic accuracy for different molecular subtypes. Immune infiltration analysis indicated significant correlations between hub genes and eight immune cell types, including B cells, effector T cells, cytotoxic T cells, regulatory T cells (Tregs), monocytes, mast cells, eosinophils, and neutrophils.</p><p><strong>Conclusions: </strong>In this study, a hypoxia-related gene signature associated with childhood asthma was identified. These findings not only highlight potential therapeutic targets for asthma but also offer new insights into its pathogenesis.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144872874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genes & genomicsPub Date : 2025-08-01Epub Date: 2025-06-16DOI: 10.1007/s13258-025-01654-7
Gang-Ho Yoon, Myeoung Su Kim, Sun-Cheol Choi
{"title":"Foxj3 represses TGF-β signals-responsive transcriptions in Xenopus early development.","authors":"Gang-Ho Yoon, Myeoung Su Kim, Sun-Cheol Choi","doi":"10.1007/s13258-025-01654-7","DOIUrl":"10.1007/s13258-025-01654-7","url":null,"abstract":"<p><strong>Background: </strong>Forkhead box (Fox) proteins belong to a large family of transcription factors characterized by a highly conserved DNA binding domain termed the 'forkhead box'. They are involved in critical functions during early development and in the adult.</p><p><strong>Objective: </strong>In this work, Foxj3 was found to regulate negatively the transcription of target genes induced by Activin/Nodal or BMP signal in Xenopus embryos. Thus, we sought to investigate the molecular mechanisms underlying this function of Foxj3 as a transcriptional repressor.</p><p><strong>Methods: </strong>Microinjection of mRNA and anti-sense morpholino oligo was employed to achieve the gain- and loss-of Foxj3 function, respectively. RT-PCR and luciferase assays were performed to investigate the effects of overexpression or knockdown of Foxj3 on TGF-β signals-responsive transcriptions. Animal cap elongation assay was used to check whether Foxj3 would affect the dorsalization of ectodermal tissues induced by Activin signal. Whole-mount in situ hybridization was carried out to analyze the in vivo expression of key marker genes in the embryos overexpressing or depleted of Foxj3.</p><p><strong>Results: </strong>Overexpression of Foxj3 was found to repress the gene responses activated by Activin/Nodal or BMP4 signals. Its increased levels also caused defective mesodermal and ectodermal specification in embryo. Conversely, knockdown of Foxj3 augmented Nodal-responsive transcription of target genes. In line with this, Foxj3 morphants displayed the malformed phenotypes resembling those of embryos exposed to increased levels of Nodal signal. Furthermore, Foxj3 repression of transcriptional responses was blocked by depletion of RNF152 or co-expression of β-catenin.</p><p><strong>Conclusion: </strong>Foxj3 functions via the RNF152/β-catenin signaling axis to repress TGF-β-dependent transcriptional responses in Xenopus early development.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"877-889"},"PeriodicalIF":1.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genes & genomicsPub Date : 2025-08-01Epub Date: 2025-06-26DOI: 10.1007/s13258-025-01656-5
Md Minarul Islam, Kyudong Han, Ye-Ji Bang, Je Chul Lee, Woo Shik Shin, Man Hwan Oh
{"title":"In silico screening of epitopes as potential vaccine candidates against pathogenic Acinetobacter baumannii.","authors":"Md Minarul Islam, Kyudong Han, Ye-Ji Bang, Je Chul Lee, Woo Shik Shin, Man Hwan Oh","doi":"10.1007/s13258-025-01656-5","DOIUrl":"10.1007/s13258-025-01656-5","url":null,"abstract":"<p><strong>Background: </strong>Multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) poses a pressing threat to global healthcare settings, as most antibiotics are ineffective against this nosocomial pathogen. Vaccines, particularly peptide-based vaccines, offer a promising and effective strategy to deal with these infections.</p><p><strong>Objective: </strong>This study aimed to evaluate the potential of epitopes derived from the OmpA protein of A. baumannii as vaccine candidates for combating this pathogen.</p><p><strong>Methods: </strong>This study employed advanced bioinformatic tools to identify potential epitopes for vaccine candidates against A. baumannii infections. IEDB and SYFPEITHI were used to identify T-cell epitopes of A. baumannii OmpA protein. The epitopes were filtered based on score, clustering, human similarity, immunogenicity, cytokine response, and safety. Epitopes with high scores and both class-I and class-II sites were selected. Three epitopes were chosen for molecular docking and physicochemical evaluation as potential vaccine candidates.</p><p><strong>Results: </strong>Three epitopes (EP1, EP2, and EP3) derived from A. baumannii OmpA were found to effectively bind with specific human leukocyte antigen (HLA) alleles. These epitopes have shown promising potential to elicit both cellular and humoral immune responses. Their physicochemical and immunological properties were thoroughly evaluated, indicating strong antigenic potential, non-toxicity, lack of allergenic properties, good binding affinity, and wide population coverage. The epitopes' two- and three-dimensional structures were predicted, and they were docked with their respective HLA alleles to assess their ability to stimulate innate immune responses. The predicted epitopes and HLA-allelic complexes exhibited excellent binding affinity, optimal Root Mean Square Deviation (RMSD) values, favorable physicochemical properties, and high-quality structural characteristics.</p><p><strong>Conclusions: </strong>This study identified epitopes that hold promise as potential solutions for combating multidrug-resistant A. baumannii, pending validation through wet lab experiments and clinical trials.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"899-909"},"PeriodicalIF":1.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144495840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}