Frontiers in Genetics最新文献

{"title":"Whole-exome sequencing reveals genetic etiology and pregnancy outcomes in fetuses with ultrasound-detected abnormalities at a tertiary center.","authors":"Meiying Cai, Na Lin, Hailong Huang, Meimei Fu, Yifang Dai, Liangpu Xu","doi":"10.3389/fgene.2026.1858421","DOIUrl":"https://doi.org/10.3389/fgene.2026.1858421","url":null,"abstract":"<p><p>Despite advances in prenatal diagnostics, the genetic causes underlying fetal ultrasound abnormalities remain poorly understood, with a significant proportion of cases lacking definitive molecular diagnoses. Invasive prenatal testing was performed in 179 cases, followed by whole-exome sequencing (WES) to identify genetic etiologies. Among 179 abnormal fetuses, 132 had single-system and 47 had multisystem abnormalities. WES identified pathogenic (P) or likely pathogenic (LP) variants in 33 cases (19 single-system, 14 multisystem), with skeletal (7), cardiac (5), and craniofacial defects (2) being most frequent. Thirty-four genes were involved, encompassing 41 variants (15 missense, 10 frameshift, 6 splicing, 6 nonsense, and 4 in-frame deletions). WES yielded a P/LP rate of 17.88% (32/179) for variants that explained the fetal phenotype, with an additional pathogenic finding (overall P/LP rate: 18.44%, 33/179). Inheritance patterns were autosomal dominant (19), recessive (12), X-linked (1), and mosaic (1). Family studies confirmed 27 variants (18 inherited, 9 <i>de novo</i>). Pregnancy outcomes included 60 terminations, 19 intrauterine deaths, and 8 postnatal abnormalities. Most fetal ultrasound phenotypes matched the disease-causing gene profiles. Combining molecular testing with ultrasound helps clinicians identify genetic causes, assess recurrence risk, and inform parents, enabling personalized management for high-risk families.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"1858421"},"PeriodicalIF":3.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13707123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149266183","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":"Linking systemic inflammation nutrition status to the tumor immune microenvironment: integrated biomarkers of neoadjuvant response in locally advanced rectal cancer.","authors":"Licong Shao, Jianting Xu, Xudong Wu, Guangliang Shao, Jiahao Chen","doi":"10.3389/fgene.2026.1948878","DOIUrl":"https://doi.org/10.3389/fgene.2026.1948878","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape of colorectal cancer (CRC), yet response remains heterogeneous. The inflammation-nutrition prognostic score (INPS), defined as the neutrophil-to-lymphocyte ratio (NLR) divided by the prognostic nutritional index (PNI), integrates systemic inflammatory burden and nutritional-immunological reserve and may provide complementary information in locally advanced rectal cancer (LARC).</p><p><strong>Methods: </strong>We retrospectively analyzed 312 patients with LARC who received standard neoadjuvant chemoradiotherapy (nCRT), with or without concurrent PD-1/PD-L1 blockade, followed by total mesorectal excision (TME). Pretreatment INPS was calculated as NLR/PNI. The primary endpoint was objective response rate (ORR); secondary endpoints included pathological complete response (pCR) and progression-free survival (PFS). ROC, logistic regression, interaction, sensitivity, and Cox analyses were performed.</p><p><strong>Results: </strong>Among 312 patients, 94 (30.1%) received ICI-containing regimens. Low INPS (<0.058) was associated with higher ORR (61.3% vs. 29.4%, P < 0.001) and pCR (38.7% vs. 11.8%, P < 0.001). INPS yielded an AUC of 0.765 (95% CI: 0.714-0.816) for ORR, compared with 0.712 for NLR, 0.668 for PNI, and 0.660 for PD-L1 CPS. In multivariable analysis, low INPS (OR = 3.31, 95% CI: 1.95-5.60, P < 0.001), MSI-H/dMMR status (OR = 4.67), PD-L1 CPS ≥ 10 (OR = 2.74), lower clinical T stage (OR = 3.15), and an ICI-containing regimen (OR = 2.55) were independently associated with response. A forced-entry disease-burden sensitivity model confirmed the association of low INPS (adjusted OR = 3.04, 95% CI: 1.74-5.30, P < 0.001).</p><p><strong>Conclusion: </strong>Low pretreatment INPS was independently associated with favorable response and PFS in LARC and provided incremental discrimination beyond MSI-H/dMMR and PD-L1 CPS. These findings support INPS as a candidate response-associated biomarker in LARC; prospective and external validation is warranted before routine clinical application.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"1948878"},"PeriodicalIF":3.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13706675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149266266","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":"The <i>COL4A3</i> c.3418+1G>T variant causes exon 39 skipping in minigene assays: functional and exploratory structural analyses.","authors":"Xuan Ban, Yue Wang, Yunshan Guo, Juan Wang, He Sun, Ping He, Mingxiu Wang, Xiaofang Tang, Qiuling Fan","doi":"10.3389/fgene.2026.1953498","DOIUrl":"https://doi.org/10.3389/fgene.2026.1953498","url":null,"abstract":"<p><strong>Background: </strong>Canonical splice-site variants are an important cause of Alport syndrome, but the transcript consequences of many heterozygous <i>COL4A3</i> variants remain experimentally unverified. We characterized <i>COL4A3</i> c.3418 + 1G>T in a 38-year-old woman with persistent isolated microscopic hematuria. Notably, the proband's mother also had microscopic hematuria but did not carry c.3418 + 1G>T, precluding supportive co-segregation.</p><p><strong>Methods: </strong>Whole-exome sequencing identified the variant, which was subsequently confirmed by Sanger sequencing. Splicing effects were assessed using SpliceAI, Pangolin, and MaxEntScan. Minigene assays were performed in HEK293T, HK-2, and human glomerular endothelial cells. Protein consequences were examined using AlphaFold-derived models, PyMOL visualization, and exploratory 5-ns molecular dynamics simulations of local α3α4α5(IV) trimer models, with additional independently initialized 20-ns replicate simulations performed as a supplementary reproducibility analysis.</p><p><strong>Results: </strong>Computational tools consistently predicted loss of the canonical donor splice site. Minigene assays demonstrated complete exon 39 skipping in all 3 cell lines, resulting in an 81-bp in-frame deletion of 27 amino acids within the α3(IV) collagenous domain. Sequence examination showed that the resulting junction preserved the Gly-X-Y register, although its protein-level structural consequences remain undetermined. Exploratory molecular dynamics analysis showed descriptive differences between wild-type and mutant models. The additional 20-ns simulations showed broadly similar RMSD ranges across independent replicates, although RMSD values varied across prespecified time blocks, indicating limited short-timescale sampling consistency. These findings were therefore considered hypothesis-generating rather than evidence of full convergence, altered stability, or impaired interchain interactions. The patient exhibited persistent isolated microscopic hematuria without proteinuria, renal dysfunction, or extrarenal manifestations, compatible with a mild autosomal dominant Alport syndrome phenotype.</p><p><strong>Conclusion: </strong><i>COL4A3</i> c.3418 + 1G>T causes complete exon 39 skipping in the tested minigene systems and a 27-amino-acid in-frame deletion. Under a conservative author-level application of the ACMG/AMP framework, PVS1_Moderate and PM2_Supporting yield a primary classification of Variant of Uncertain Significance (VUS); PP4 was not applied in the primary classification because isolated microscopic hematuria has limited specificity and the maternal phenotype was discordant. A Likely Pathogenic classification is retained only as a conditional author-level alternative if PVS1 (RNA) is calibrated to Strong and PP4 is applied.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"1953498"},"PeriodicalIF":3.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13706678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149266213","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":"A modular verification and validation framework for hybrid-capture next-generation sequencing HLA typing in clinical histocompatibility laboratories.","authors":"Alice Scarpa, Diego Ferrarese, Samantha Guidotti, Veronica Scaglia, Angela Rossi","doi":"10.3389/fgene.2026.1959391","DOIUrl":"https://doi.org/10.3389/fgene.2026.1959391","url":null,"abstract":"<p><p>Hybrid-capture next-generation sequencing HLA workflows are increasingly used in clinical histocompatibility laboratories for high-resolution HLA typing. Compared with amplicon-based approaches, they may provide broader coverage of HLA genes, improved ambiguity resolution and the possibility of including additional targets; however, their greater analytical, bioinformatic and interpretative complexity requires a clear definition of intended use, reportable scope and required validation level. A practical and modular framework was developed for the verification and validation of hybrid-capture next-generation sequencing HLA workflows, applicable to IVDR-regulated methods used according to the manufacturer's instructions for use, locally adapted IVDR workflows, research-use-only workflows converted to clinical use, laboratory-developed or laboratory-adapted workflows and outputs not fully covered by manufacturer claims. Core modules required for clinical HLA typing are distinguished from additional modules activated by specific claims or local adaptations, including analytical performance, bioinformatic validation, risk management and reporting governance. It provides an operational pathway to document fitness for intended use and to distinguish clinically reportable results from technically available outputs not validated for diagnostic use. A dataset generated under routine conditions using a commercial full-length HLA capture-based workflow is used as a practical implementation example. A modular structure integrating analytical performance, bioinformatic control, risk-based thinking, reporting governance and continuous monitoring is provided by this framework in clinical immunogenetics and histocompatibility laboratories.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"1959391"},"PeriodicalIF":3.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13696030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149266260","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":"Cross-lineage anomaly detection of microRNA expression: a framework for deriving exploratory candidate biomarkers in sarcoma.","authors":"Mritunjoy Dey, Piotr Remiszewski, Ewelina Perdas, Paweł Golik, Jakub Piątkowski, Anna M Czarnecka","doi":"10.3389/fgene.2026.1907450","DOIUrl":"https://doi.org/10.3389/fgene.2026.1907450","url":null,"abstract":"<p><strong>Introduction: </strong>Sarcomas are rare, heterogeneous malignancies of mesenchymal origin whose diagnosis and molecular classification remain challenging. We introduced a oneclass anomaly detection framework to microRNA expression profiles to test whether sarcoma-associated miRNA features are distinguishable from those of epithelial, haematological, and neurological cancers and if these features carry any biological relevance.</p><p><strong>Methods: </strong>Candidate miRNAs meeting cross-lineage significance criteria were further evaluated through differential expression analysis against subtype-matched normal mesenchymal reference tissue, pathway enrichment, and survival analysis. A five-miRNA index (\"Index 5\"), derived by Fisher's linear discriminant analysis with leave-one-out cross-validation in a TCGA-SARC training cohort, was applied without refitting to an independent external cohort (GSE36982).</p><p><strong>Results: </strong>The five-miRNA index (\"Index 5\") achieved an AUC of 0.93 and, applied without refitting to an independent external cohort (GSE36982), an AUC of 0.97. After Benjamini-Hochberg correction, one candidate miRNA (miR-1305) remained significantly associated with overall survival.</p><p><strong>Discussion: </strong>These findings identify a computationally derived, externally tested candidate miRNA signature associated with sarcoma. While this study lacks experimental and clinical validation, the broader aim of this study was to come up with a framework that would assist and speedup the exploratory candidate biomarker discovery process in rare malignancies.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"1907450"},"PeriodicalIF":3.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13696034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149266063","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":"Global trends and hotspots of genetic research on non-syndromic cleft lip with or without cleft palate: a bibliometric and bioinformatics analysis.","authors":"Yuxuan Shang, Mingjian Zhao, Shuangshuang Gao, Shikang Gao, Mengru Zhu","doi":"10.3389/fgene.2026.1907333","DOIUrl":"https://doi.org/10.3389/fgene.2026.1907333","url":null,"abstract":"<p><strong>Background: </strong>Non-syndromic cleft lip with or without cleft palate (NSCL/P) accounts for 70% of orofacial cleft cases worldwide and causes physical dysfunction and psychological burden. Prior bibliometric studies have outlined the general NSCL/P research landscape; however, a systematic overview targeting the genetic dimension, evolutionary trends since the Human Genome Project, and dual-database cross-validation remains limited. This study mapped the global bibliometric landscape of NSCL/P genetics, identified shifting research paradigms, and functionally validated candidate genes through bioinformatic analyses of environmental risk factors.</p><p><strong>Methods: </strong>Publications from January 1990 to 31 January 2026, were retrieved from the Web of Science Core Collection and analyzed using bibliometric tools, including R-Bibliometrix, VOSviewer, and CiteSpace. Subsequently, Scopus publications were searched using the same search strategy for cross-validation. Finally, toxicant-induced and NSCL/P-related genes were screened from the GeneCards database to identify overlapping targets, followed by construction of a protein-protein interaction network and Kyoto Encyclopedia of Genes and Genomes enrichment analysis to characterize potential functional pathways.</p><p><strong>Results: </strong>A total of 1,511 eligible publications were analyzed, covering 86 countries and regions, 1,766 institutions, 6,061 authors, and 383 journals, with rapid publication growth observed between 2018 and 2021. The United States led in output and citations alongside the University of Iowa and Murray, Jeffrey C., as key contributors. Keyword clustering categorized the current studies into four major categories: genetic analysis methodologies, developmental biology and phenotypes, epidemiology and environmental factors, and molecular regulatory mechanisms. Alcohol- and nicotine-induced overlapping pathogenic genes were identified with enriched pathways involved in the regulation of embryonic craniofacial development, cell proliferation, and apoptosis.</p><p><strong>Conclusion: </strong>This study clarified the publication trends, key research forces, disciplinary distributions, and hotspots in NSCL/P genetics, revealing an ongoing shift in research focus. In silico network analyses of public databases identified distinct molecular pathways mediating alcohol- and nicotine-induced developmental disorders. These findings provide reliable evidence for future mechanistic exploration of NSCL/P pathogenesis.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"1907333"},"PeriodicalIF":3.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13696031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149266184","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":"Multi-model genome-wide association analysis reveals natural allelic variation and candidate loci for kernel phytic acid content in quality protein maize.","authors":"Sushil Kumar, Sourabh Kumar, Dinesh Kumar Saini, Rainy Rainy, Abhijit Kumar Das, Chikkappa G Karjagi, Dharampaul Chaudhary, Shailendra Singh Gaurav, Ramesh Kumar","doi":"10.3389/fgene.2026.1925511","DOIUrl":"https://doi.org/10.3389/fgene.2026.1925511","url":null,"abstract":"<p><p>Phytic acid (PA) is the major phosphorus-storage compound in maize kernels, but its strong mineral-chelating capacity limits the bioavailability of essential nutrients in humans and monogastric animals. Although classical low-phytic-acid mutants have demonstrated the feasibility of phytate reduction, their use in breeding has been constrained by pleiotropic effects on seed viability, germination, and agronomic performance. Therefore, identifying natural allelic variation for kernel PA content in elite nutritional backgrounds such as Quality Protein Maize (QPM) is important for biofortification breeding. To our knowledge, no genome-wide association study has yet been reported for kernel PA content in maize. Here, we evaluated 249 QPM inbred lines across two environments and conducted genome-wide association analysis using sequencing-derived SNP markers. Kernel PA content showed substantial phenotypic variation, highly significant genotypic effects, and high broad-sense heritability in both environments, indicating strong genetic control. Of 11,525,180 variants initially called, 115,416 chromosomal biallelic SNPs passed initial filtering, and 26,074 high-quality SNPs were retained for population structure, linkage disequilibrium, and association analyses. Multi-model GWAS identified five high-confidence marker-trait associations on chromosomes 1, 3, 4, and 7. The strongest locus, chr3:236714544, was consistently detected across environments and analytical models and explained up to 17.7% of phenotypic variation. Allelic effect analysis confirmed significant differences among genotype classes at all five loci, with the clearest differentiation observed at chr3:236714544. LD-based haplotype analysis identified a three-SNP chromosome four haplotype block associated with kernel PA variation, with Hap2/GAC showing lower PA content. Integrated candidate-gene analysis prioritized seven putative candidate genes involved in transcriptional regulation, phosphate transport, phosphorylation-dependent signaling, seed development, and lipid/protein storage-related processes. <i>Zm00001eb163880</i> emerged as the strongest candidate gene at the major chr3:236714544 locus, supported by a predicted missense variant and strong seed-related expression. Together, these results identify robust genomic loci, favorable allelic variation, and prioritized candidate genes for kernel PA content, providing a foundation for marker-assisted selection and future validation toward developing QPM maize with reduced anti-nutritional burden and improved mineral bioavailability.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"1925511"},"PeriodicalIF":3.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13696032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149266208","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":"MicroRNA cargo of extracellular vesicles as mediators of immune dysregulation in pediatric immune thrombocytopenia: from pathogenetic drivers to biomarkers.","authors":"Lucia Argenziano, Maria Maddalena Marrapodi, Giuseppe Di Feo, Oriana Di Domenico, Francesca Rossi, Alessandra Di Paola","doi":"10.3389/fgene.2026.1951187","DOIUrl":"https://doi.org/10.3389/fgene.2026.1951187","url":null,"abstract":"<p><p>Pediatric immune thrombocytopenia (ITP) is an acquired autoimmune disorder, caused by the production of autoantibodies against platelets which leads to thrombocytopenia. It is characterized by profound alterations in both inflammatory and immune profiles. In this context, the role of microRNAs (miRNAs) as post-transcriptional regulators of immunity and the function of extracellular vesicles (EVs) as key mediators of intercellular communication are two fundamental aspects for understanding ITP pathophysiology. In ITP, altered miRNA expression disrupts immune tolerance, lymphocyte subtype differentiation and platelet production. miRNAs are incorporated into EVs and transferred to recipient cells, which confers greater stability to the miRNAs. To date, the interaction between miRNAs and EVs in pediatric ITP has been relatively understudied. In this review, we examine the landscape of dysregulated miRNAs in ITP, focusing in particular on their role in immune dysregulation and on the contribution of EVs as carriers of pathogenic miRNAs. The relationship between EVs and miRNAs could facilitate the development of non-invasive diagnostic tools and EV-based therapeutic strategies designed to reestablish immune homeostasis in pediatric ITP.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"1951187"},"PeriodicalIF":3.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13696033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149266232","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":"Economic impact of biomarker-based aging interventions on healthcare costs and individual value.","authors":"Federico Felizzi","doi":"10.3389/fgene.2026.1814599","DOIUrl":"https://doi.org/10.3389/fgene.2026.1814599","url":null,"abstract":"<p><p>We investigate the economic impact of controlling the pace of aging through biomarker monitoring and targeted interventions. Using the DunedinPACE epigenetic clock as a measure of biological aging rate, we model how different intervention scenarios affect frailty trajectories and their subsequent influence on healthcare costs, lifespan, and health quality. Our model demonstrates that controlling DunedinPACE from age 50 onward can reduce frailty prevalence, resulting in cumulative healthcare savings of up to CHF 131,608 per person over 40 years in our most optimistic scenario. From an individual perspective, the willingness to pay for such interventions reaches CHF 3.2 million in the most optimistic scenario when accounting for both extended lifespan and improved health quality. When the direct cost of epigenetic testing is included, the healthcare-system case is sensitive to test price and testing frequency, whereas the individual-value case remains strongly positive. These findings suggest substantial economic value in technologies that can monitor and modify biological aging rates, providing evidence for both healthcare systems and consumer-focused business models in longevity medicine.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"1814599"},"PeriodicalIF":3.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13696027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149266182","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":"Saliva-based genomic signatures for early detection of oral squamous cell carcinoma: the state and perspectives of translation.","authors":"Hiren Hansraj Patadiya, Satya Upadhyayula, Vrunda T Adeshara","doi":"10.3389/fgene.2026.1831378","DOIUrl":"https://doi.org/10.3389/fgene.2026.1831378","url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) is one of the leading causes of cancer morbidity and mortality globally, and prognosis is closely related to the stage at diagnosis. Although advances in surgery, radiotherapy, and systemic therapies have improved outcomes, late presentation remains a major limitation to survivability. Saliva has emerged as a promising noninvasive diagnostic biofluid due to its proximity to tumors, ease of repeated collection, and the presence of tumor-derived nucleic acids. From 2020 to 2024, research increasingly focused on integrated genomic signatures combining somatic mutations, DNA methylation patterns, and RNA-based biomarkers (including mRNA, microRNA, and other noncoding RNAs) in whole saliva, cell-free fractions, and extracellular vesicles. Technological advancements such as digital polymerase chain reaction (PCR), targeted next-generation sequencing, and computational modeling have enhanced sensitivity for detecting low-abundance tumor signals and enabled longitudinal monitoring strategies. However, translation into routine clinical practice remains limited because of pre-analytical heterogeneity, inflammatory confounding, batch effects, late-stage enriched cohorts, and lack of large prospective multicenter validation. This review synthesizes current evidence, evaluates analytical and clinical readiness, and proposes a translational roadmap for clinical integration.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"17 ","pages":"1831378"},"PeriodicalIF":3.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13691244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149266242","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}