Frontiers in Genetics最新文献

{"title":"Genetic associations in the gut-lung axis: a Mendelian randomization study and <i>in vitro</i> assessment of sodium butyrate in non-small cell lung cancer.","authors":"Weili Yi, Li Qin, Dongning Huang, Fang Wu","doi":"10.3389/fgene.2026.1900040","DOIUrl":"https://doi.org/10.3389/fgene.2026.1900040","url":null,"abstract":"<p><strong>Background: </strong>The gut microbiota may influence host immunity, but the relationship between specific microbial genera and non-small cell lung cancer (NSCLC) risk remains uncertain. We evaluated genetically proxied microbial abundance and conducted separate exploratory experiments with sodium butyrate (NaB).</p><p><strong>Methods: </strong>Two-sample Mendelian randomization (MR) used genus-level MiBioGen summary statistics and FinnGen/OpenGWAS NSCLC data (finn-b-C3_LUNG_NONSMALL; 1,627 cases and 217,165 controls). Instruments were selected at P < 1 × 10^-5 with linkage disequilibrium clumping (r² < 0.001; 10,000 kb) and F > 10. Inverse variance weighting (IVW) was the primary estimator; Benjamini-Hochberg false discovery rate (BH-FDR) correction was applied across 119 genera. Sensitivity analyses included MR-Egger, weighted median, mode-based methods, heterogeneity, pleiotropy and leave-one-out analyses. NaB, used as a representative microbial metabolite rather than a taxon-specific product, was evaluated at 1 mM for 24 h in tumor-conditioned medium (TCM) experiments.</p><p><strong>Results: </strong>Six genera showed nominal inverse IVW associations with NSCLC risk (P = 0.0120-0.0498): Alistipes, Methanobrevibacter, <i>Bacteroides</i>, Ruminococcus gauvreauii group, Ruminococcus 1 and <i>Peptococcus</i>. None survived BH-FDR correction (q = 0.6072-0.9819). Sensitivity tests did not detect heterogeneity or directional pleiotropy for these genera, but alternative estimators and leave-one-out analyses did not consistently retain nominal significance. In THP-1-derived macrophages, NaB treatment altered polarization-associated transcripts, reduced the TCM-associated CCK-8 signal and increased acetylated histone H3 (Ac-H3) relative to TCM alone.</p><p><strong>Conclusion: </strong>The MR analysis identifies six suggestive microbial associations with NSCLC risk that require independent replication. Complementary NaB experiments show changes in macrophage-associated transcripts, metabolic viability and histone acetylation, providing a basis for further study of microbial metabolites in the tumor microenvironment.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"1900040"},"PeriodicalIF":3.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13719139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149296881","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":"Causal associations between gut microbiota and autism spectrum disorder and attention-deficit/hyperactivity disorder: a two-sample mendelian randomization study.","authors":"Shangyun Shi, Ancha Baranova, Hongbao Cao, Fuquan Zhang","doi":"10.3389/fgene.2026.1972696","DOIUrl":"https://doi.org/10.3389/fgene.2026.1972696","url":null,"abstract":"<p><strong>Background: </strong>The gut microbiota have been implicated in the development of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). However, the precise causal relationships between the gut microbiota and ASD or ADHD remain unclear.</p><p><strong>Methods: </strong>We investigated potential causal associations between gut microbiota and two neurodevelopmental mental disorders (ASD and ADHD) via Mendelian randomization (MR) analyses. We used genome-wide association study (GWAS) summary datasets, including data from the MiBioGen consortium (N = 18,340), the Dutch Microbiome Project (N = 8,208), an ASD GWAS (N = 46,350), and an ADHD GWAS (N = 292,548).</p><p><strong>Results: </strong>Our MR analysis identified 16 gut bacterial taxa associated with ASD. Seven taxa were associated with an increased risk (OR 1.03-1.10), while nine were associated with a decreased risk (OR 0.89-0.96). Conversely, 28 gut bacterial taxa were causally linked to ADHD: 16 were associated with an increased risk (OR 1.02-1.04), and 12 were associated with a decreased risk (OR 0.95-0.98). Both ASD and ADHD were causally influenced by the family \"Clostridiales noname,\" but with opposite effects.</p><p><strong>Conclusion: </strong>Our MR analysis revealed causal effects of specific gut microbiota on ASD and ADHD, suggesting that certain gut microbes may play a role in the development and treatment of these disorders, as well as in their differential diagnosis.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"1972696"},"PeriodicalIF":3.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13719141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149296929","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":"Adult presentation of SLC29A3-related disorder spectrum with marked hypogammaglobulinemia due to a recurrent homozygous pathogenic variant (G437R): a case report.","authors":"Mohammad Ameen Ishqair, Abbas K H Masalma, Mohanad Saleh, Fawaz Awad, Aliaa Khalili, Anas Ameen Ishqair, Somaya Salah, Abed-Rahman N Saleh","doi":"10.3389/fgene.2026.1904219","DOIUrl":"https://doi.org/10.3389/fgene.2026.1904219","url":null,"abstract":"<p><strong>Background: </strong>SLC29A3-related disorder spectrum encompasses rare autosomal recessive conditions characterized by multisystem involvement, including immunodeficiency, lymphoproliferation, cutaneous findings, endocrine dysfunction, and growth failure. The clinical presentation is highly heterogeneous, often leading to delayed diagnosis, particularly in adults.</p><p><strong>Case presentation: </strong>A 33-year-old Palestinian woman born to consanguineous parents presented with a lifelong history of recurrent severe respiratory infections, growth failure (short stature and microcephaly), recurrent nephrolithiasis, chronic vomiting, generalized hirsutism, and bilateral hallux valgus. Laboratory evaluation revealed marked hypogammaglobulinemia (IgG <320 mg/dL, IgA <25 mg/dL, IgM <25 mg/dL), microcytic anemia, and severe vitamin D deficiency. Imaging confirmed chronic pulmonary small-airway changes and a chronically small right kidney with recurrent stones. Whole-exome sequencing identified a homozygous pathogenic SLC29A3 variant (c.1309G>A; p.Gly437Arg), establishing a diagnosis within the SLC29A3-related disorder spectrum. This case is unique due to its adult presentation, the exceptional severity of the humoral immunodeficiency, and the associated renal manifestations, which are infrequently reported in this spectrum.</p><p><strong>Conclusion: </strong>This report underscores the importance of considering SLC29A3-related disorder spectrum in adults with multisystem disease. Recognition of this spectrum enables targeted multidisciplinary care, including immunoglobulin replacement therapy and anticipatory surveillance for endocrine and renal complications.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"1904219"},"PeriodicalIF":3.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13719138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149296926","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":"Single-cell and bulk transcriptomic characterization of the osteosarcoma microenvironment reveals lineage-specific programs and inflammatory differences associated with metastasis.","authors":"Zhiwen Zhou, Zhijun Li","doi":"10.3389/fgene.2026.1927885","DOIUrl":"https://doi.org/10.3389/fgene.2026.1927885","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Osteosarcoma is a heterogeneous bone malignancy in which malignant, immune, stromal, and bone-lineage cells form a complex microenvironment. Clinical activity of immune-checkpoint blockade has remained limited in advanced osteosarcoma, motivating cell-type-resolved investigation of the tumor microenvironment while avoiding mechanistic overinterpretation of cross-sectional transcriptomic data.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Single-cell RNA-sequencing data from primary osteosarcoma were obtained from GEO (GSE162454; six patients) and analyzed with Scanpy using quality filtering, normalization, highly variable gene selection, principal component analysis, neighborhood graph construction, UMAP, Leiden clustering, and marker-based cell-type annotation. Seven transcriptional programs and ligand-receptor communication scores were evaluated. An independent bulk osteosarcoma cohort with metastatic status and overall survival annotation (GSE21257; n = 53) was used for differential expression, cross-platform comparison, and survival analysis. RT-qPCR was performed in primary human osteoblasts exposed to MG-63 osteosarcoma-conditioned medium.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;After quality control, 44,189 cells with 25,473 detected genes were retained. Leiden clustering resolved 23 clusters annotated into 11 cell types; myeloid cells (34.0%) and osteoblasts (16.6%) were the largest populations. Osteoblasts showed the highest osteogenic program scores, whereas myeloid cells showed the highest inflammatory and immune-evasion scores. Reclustering of osteoblasts, osteocytes, and mesenchymal stromal cells resolved seven stromal subclusters, but pairwise co-expression between representative osteogenic and inflammatory genes was generally weak. Ligand-receptor analysis highlighted MIF-CD74, SPP1-CD44, and SPP1-ITGAV as the strongest scored interactions. In GSE21257, 333 genes differed between metastatic and non-metastatic tumors at FDR&lt;0.05; the inflammatory module was lower in metastatic tumors, whereas the osteogenic module was not significantly different. The single-cell osteoblast effect showed only modest concordance with the bulk metastatic effect (Spearman rho = 0.254), and a 20-gene osteoblast signature did not stratify overall survival (log-rank p = 0.968). &lt;i&gt;In vitro&lt;/i&gt;, osteosarcoma-conditioned medium reduced RUNX2 and SP7 and increased SOST and RANKL expression in primary osteoblasts.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Integrated single-cell and bulk transcriptomic analyses identify lineage-specific osteogenic, inflammatory, and communication programs in osteosarcoma but also demonstrate limited cross-platform generalizability of osteoblast-centered signatures. The RT-qPCR experiment supports an osteoblast transcriptional response to soluble factors from MG-63 cells, but it does not establish a specific immunosuppressive mechanism or prognostic biomarker. These findings should therefore be considered hypothesis-generatin","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"1927885"},"PeriodicalIF":3.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13719136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149296902","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":"Biobanking across Africa: from participant-level trust to institutional trustworthiness.","authors":"Aisha Sallah, Salma Tarmoun, Krishna Gajjar, Patience Yeboah, Bernard Abakah, Everlyne Mutua, Dimitris Boufidis","doi":"10.3389/fgene.2026.1953975","DOIUrl":"https://doi.org/10.3389/fgene.2026.1953975","url":null,"abstract":"<p><p>Building trust and maintaining participant engagement are widely recognized as requirements for sustainable biobanking. Yet efforts to achieve these goals must account for the historical, economic, geo-political and socio-cultural contexts that shape participant engagement. In Africa, biobanking has shown immense scientific and global public health value, but persistent governance challenges continue to affect participation. In this Perspective, we examine the factors that have constrained participant engagement in biobanking across Africa. We argue that trust is not simply a participant-level deficit to be corrected through increased outreach. Instead, trust and mistrust are shaped by the broader biobanking ecosystem, and by whether its institutions have demonstrated that they are worthy of public trust. Drawing on studies from across the continent, we propose strategies for how governance bodies, researchers and healthcare professionals can develop biobanking systems and frameworks that are sustainable and accountable to the public at both the national and international levels. Importantly, we identify science diplomacy as a valuable mechanism for strengthening cross-border coordination in support of more equitable, coherent and locally-governed biobanking initiatives.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"1953975"},"PeriodicalIF":3.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13719140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149296893","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: Advanced genetic and genomic methods and applications for malaria surveillance.","authors":"Shazia Ruybal-Pesántez, Johanna H Kattenberg, Anita Ghansah, Sarah Auburn","doi":"10.3389/fgene.2026.2000967","DOIUrl":"https://doi.org/10.3389/fgene.2026.2000967","url":null,"abstract":"","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"2000967"},"PeriodicalIF":3.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13716506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149296867","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":"Cell-type-resolved colocalisation prioritises <i>KCNIP2</i> as a candidate epilepsy drug-target detectable at inhibitory-neuron but not bulk-tissue resolution: a Mendelian randomisation and colocalisation study.","authors":"Aytac Gul","doi":"10.3389/fgene.2026.1920945","DOIUrl":"https://doi.org/10.3389/fgene.2026.1920945","url":null,"abstract":"<p><p>Most antiseizure medicines act on a limited set of neuronal targets. Approximately a third of patients have treatment-resistant epilepsy, creating a need for mechanistically distinct drug targets. Human genetics can prioritise them, but epilepsy target-discovery has measured expression in plasma or bulk brain tissue and has yielded inconsistent candidate lists. Common-variant association for generalised epilepsy is enriched in neuronally expressed genes, so the cell type measured may determine which druggable targets are detectable. Genes at the genome-wide significant loci of the largest epilepsy meta-analysis were assessed by drug-target Mendelian randomisation (MR). A gene was retained only where the expression and disease signals colocalised on a single causal variant at a posterior probability above 0.8. Each gene was assessed across inhibitory neurons, excitatory neurons, four glial cell types, and bulk cortex, with fine-mapping and directional testing in FinnGen. Of the 23 prioritised genes screened, MR nominated ten and colocalisation retained 2. <i>KCNIP2</i> colocalised with generalised epilepsy above the threshold in inhibitory neurons alone. Higher expression was associated with lower risk (posterior 0.95, odds ratio (OR) 0.64, and <i>p</i> = 2.5 × 10^-11), with a weaker, directionally concordant sub-threshold signal in oligodendrocytes (posterior 0.53). The colocalising variant is shared with the neighbouring <i>CUEDC2</i> (<i>r</i> ² = 0.975), so the two genes cannot be separated on genetic evidence alone. In the bulk cortex, <i>KCNIP2</i> carried a strong expression signal mapping to a different causal variant, with no colocalisation. <i>AP3D1</i> colocalised across inhibitory neurons, excitatory neurons, and bulk cortex for generalised epilepsy and was associated with increased risk (OR 1.46). Both directions reproduced at the matched generalised-epilepsy endpoint in FinnGen, where <i>KCNIP2</i> was protective and <i>AP3D1</i> was risk-increasing. The colocalisation did not reproduce there, so FinnGen supports the direction of effect and not the shared-variant evidence. In epilepsy, the cellular compartment in which expression is measured can determine whether a drug-target signal is detected, so analyses restricted to plasma or bulk tissue may miss cell-type-restricted targets such as <i>KCNIP2</i>. The demonstration rests on this single locus. Cell-type-resolved colocalisation prioritises <i>KCNIP2</i>, which cannot be separated from <i>CUEDC2</i>, as a candidate for functional investigation, with <i>AP3D1</i> being a genetically supported but pharmacologically intractable second locus.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"1920945"},"PeriodicalIF":3.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13713021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149286536","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":"Machine learning, molecular docking, and experimental validation identify shared molecular signatures between idiopathic pulmonary arterial hypertension and malignant pleural mesothelioma: a retrospective study.","authors":"Neng Zhang, Chunyu Wang, Rui Wang, Xue Guo, Jing Yu, Jie Wang, Qin Luo, Yun Wu","doi":"10.3389/fgene.2026.1894027","DOIUrl":"https://doi.org/10.3389/fgene.2026.1894027","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic pulmonary arterial hypertension (IPAH) exhibits cancer-like features, yet its pathogenesis remains unclear. Given molecular similarities between IPAH and malignant pleural mesothelioma (MPM), this study aimed to uncover shared transcriptomic patterns.</p><p><strong>Methods: </strong>GEO datasets for IPAH and MPM were analyzed. Overlapping DEGs and WGCNA modules were identified. PPI network analysis combined with LASSO, random forest, and SVM-RFE was used to identify candidate biomarker genes. A classification model was constructed and evaluated using leave-one-out cross-validation and bootstrap optimism correction. Immune infiltration was evaluated by ssGSEA. Molecular docking and MD simulations assessed drug binding to candidate target proteins. qRT-PCR validated candidate biomarker gene expression.</p><p><strong>Results: </strong>Six concordantly upregulated and eleven concordantly downregulated DEGs were shared between IPAH and MPM. Upregulated genes were enriched in cell cycle regulation, while downregulated genes were enriched in neutrophil chemotaxis. WGCNA identified 58 overlapping genes. CXCR2, S100A9, and LCN2 were identified as candidate biomarker genes. A ROTS sensitivity analysis confirmed that all 1710 MPM DEGs were reproducible and directionally concordant at the matching FDR <0.05 threshold despite the imbalanced case-control ratio. The classification model achieved AUCs of 0.909 and 0.875 in training and external validation sets, with a LOOCV AUC of 0.879 and an optimism-corrected AUC of 0.896. Immune infiltration revealed increased Th17 cells but decreased neutrophils in IPAH. CXCR2 and S100A9 expression correlated with neutrophil infiltration; LCN2 expression correlated with metabolic reprogramming. Navarixin showed the strongest binding affinity to CXCR2 (-10.1 kcal/mol). MD simulations confirmed stable binding of the CXCR2-Navarixin complex. qRT-PCR confirmed significant downregulation of all three genes in IPAH patients.</p><p><strong>Conclusion: </strong>This hypothesis-generating study identifies shared transcriptomic signatures between IPAH and MPM, highlighting CXCR2, S100A9, and LCN2 as candidate biomarkers linked to immune dysregulation and metabolic reprogramming. The computational and correlative nature of these findings, together with the limited size of the external validation cohort, requires confirmation through functional experiments and validation in larger, independent, and multicentre cohorts before clinical translation can be considered.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"1894027"},"PeriodicalIF":3.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13713174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149286469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Tumor-immune microenvironment and nutritional status biomarkers predict recurrence after total colectomy for locally advanced colon cancer: development and internal validation of a nomogram.","authors":"Yanhui Yang, Meng Gao, Songchun Liu, Qiong Yang","doi":"10.3389/fgene.2026.1998945","DOIUrl":"https://doi.org/10.3389/fgene.2026.1998945","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fgene.2026.1916575.].</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"1998945"},"PeriodicalIF":3.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13713172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149286508","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":"Perioperative immunogenomics and clinical outcomes under ERAS-based nursing care in muscle-invasive bladder cancer.","authors":"Lu-Lu Xin, Jin-Jin Guo, Xin-Ying Zheng, Zhao-Yang Li","doi":"10.3389/fgene.2026.1967034","DOIUrl":"https://doi.org/10.3389/fgene.2026.1967034","url":null,"abstract":"<p><strong>Background: </strong>Surgical trauma is associated with perioperative immune perturbation in muscle-invasive bladder cancer (MIBC). Enhanced Recovery After Surgery (ERAS) combines multidisciplinary perioperative management with structured nursing care, but its immunogenomic associations remain incompletely characterized.</p><p><strong>Methods: </strong>This retrospective historical-control cohort included 126 MIBC patients undergoing radical cystectomy with Bricker ileal conduit (ERAS-based care, n = 63; conventional care, n = 63). Serial peripheral immune profiling was performed at T0 (preoperative), T1 (24 h postoperative), and T2 (POD7/discharge). Tumor analyses included multiplex immunofluorescence, tumor mutational burden (TMB), and NanoString immune-gene profiling; spatial transcriptomics was performed in 24 specimens (12/group). Clinical outcomes included 30-day infectious complications and survival, while biomarker and immunogenomic analyses were considered exploratory.</p><p><strong>Results: </strong>ERAS-based care was associated with a less pronounced postoperative CD8⁺ T-cell decline (22.8% vs. 41.6%, P < 0.001) and lower T1 serum IL-6 (43.2 vs. 87.4 pg/mL, P < 0.001). An exploratory four-marker T1 immune index (CD8⁺ count, IL-6, sPD-L1, and NK activity) showed predictive performance for 30-day infectious complications (AUC = 0.84, 95% CI 0.76-0.92). In resection specimens, the ERAS cohort had a higher proportion of the immune-inflamed tumor immune microenvironment (TIME) phenotype (52.4% vs. 28.6%, P = 0.012). Exploratory survival analyses also identified associations with an eight-gene immune signature and TMB status; these findings require validation.</p><p><strong>Conclusion: </strong>In this retrospective cohort, ERAS-based perioperative nursing and multidisciplinary care were associated with differences in systemic immune recovery, postoperative outcomes, and cross-sectional tumor immune features. The proposed immune-marker and gene-signature findings are exploratory and require independent validation before clinical implementation.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"1967034"},"PeriodicalIF":3.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13713013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149286457","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}