Human Genomics最新文献

{"title":"Re: \"A novel splice-altering frameshift variant in the COL1A1 gene underlies osteogenesis imperfecta type I: molecular characterization of a four-generation Chinese pedigree and literature review\".","authors":"Raymond Dalgleish","doi":"10.1186/s40246-026-00990-3","DOIUrl":"10.1186/s40246-026-00990-3","url":null,"abstract":"<p><p>A paper entitled \"A novel splice-altering frameshift variant in the COL1A1 gene underlies osteogenesis imperfecta type I: molecular characterization of a four-generation Chinese pedigree and literature review\" was recently published in this journal. Unfortunately, it contains a number of errors that the authors should correct. The most serious errors are incorrect sequence variant descriptions and inappropriate use of AI-assisted protein structure prediction.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"20 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13192231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147987345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The diabetes exposome: interplay of environmental and genetic determinants in diabetes.","authors":"Bushra Zia, Juma AlKaabi, Adnan Agha, Charu Sharma, Bassam R Ali","doi":"10.1186/s40246-026-00987-y","DOIUrl":"10.1186/s40246-026-00987-y","url":null,"abstract":"<p><p>Diabetes mellitus arises from complex interactions between biological susceptibility and diverse environmental influences that extend beyond traditional \"genes versus lifestyle\" models. The exposome is defined as the aggregate of non-genetic environmental exposures and their biological consequences across the life course. It provides a systems-level framework to evaluate this interaction, spanning chemical, physical, social, and behavioral domains while integrating them with internal molecular responses to decode how environments shape metabolic health. Emerging assessment strategies, including exposome-wide association studies (ExWAS), high-resolution mass spectrometry-based biomonitoring, geospatial and remote-sensing platforms, and wearable exposure sensors, enable characterization of multi-exposure profiles rather than single agents in isolation. Within exposome domains, air pollution, endocrine-disrupting chemicals, food-borne contaminants, exposome characteristics of the built environment, and chronic psychosocial stress have each been shown to contribute to the development and progression of both type 1 and type 2 diabetes. These diverse exposures often share common pathogenic mechanisms of chronic low-grade inflammation, oxidative and nitrosative stress, alterations in the gut microbiome, and epigenetic changes that ultimately lead to glucose dysregulation. Recent progress in metabolomics, lipidomics, and epigenomics is elucidating the \"internal exposome,\" providing molecular fingerprints that encode prior exposure and detect early metabolic disruption. This integrated approach argues for a paradigm adjustment in diabetes prevention from behavior-centered strategies to those that also target upstream environmental determinants. Exposomic information can improve risk prediction, inform precision public health and medical practice, and inform policy regarding air pollution, chemical use, urban planning, and food systems. This review summarizes the current state of knowledge of the exposome in diabetes, describing its conceptual underpinnings, major tools of assessment, major epidemiologic findings, and biological mechanisms, and identifying the key challenges and opportunities for exposomics to inform effective approaches to diabetes prevention and planetary health.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13366953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning-driven identification of circulating biomarkers and therapeutic compounds for diabetic retinopathy.","authors":"Di Chen, Guanrong Wu, Shuoxin Liao, Haoxian Zhu, Fangfang Li, Chang Liu, Hongyue Zhao, Qianli Meng, Xiang Fang","doi":"10.1186/s40246-026-00967-2","DOIUrl":"https://doi.org/10.1186/s40246-026-00967-2","url":null,"abstract":"<p><strong>Background: </strong>Diabetic retinopathy (DR) is a major cause of severe visual impairment, where early diagnosis and intervention are crucial to prevent irreversible damage. Given that obtaining biomarkers from ocular fluids is highly invasive, we here leverage bioinformatic approaches to identify novel biomarkers and potential therapeutic drugs in the peripheral blood of patients with DR.</p><p><strong>Methods: </strong>The GSE221521 dataset, derived from peripheral blood leukocytes, was analyzed to identify differentially expressed genes (DEGs) among controls, diabetes mellitus (DM) and DR patients, with subsequent gene set enrichment analysis (GSEA). Weighted gene co-expression network analysis (WGCNA) was applied to screen DR-associated modules. Key genes were further filtered via protein-protein interaction (PPI) network and support vector machine-recursive feature elimination (SVM-RFE). Two SVM diagnostic models based on these key genes were constructed, trained on the GSE221521 training set, and validated on the test set using receiver operating characteristic (ROC) curve analysis. The potential of the identified key genes as diagnostic biomarkers was further verified in independent clinical samples. Immune infiltration patterns were compared across the three groups. Finally, potential therapeutic compounds for DR were predicted via Connectivity Map (CMap) and molecular docking.</p><p><strong>Results: </strong>Differential expression analysis of the GSE221521 dataset identified 635 DEGs. GSEA showed that upregulated DEGs in DR patients (vs. DM) were significantly enriched in the MAPK, Insulin and VEGF signaling pathways. WGCNA identified the green and magenta modules as the top DR-associated modules, from which four (FLNA, TSC22D4, U2AF2, and HCFC1) and two (NUDC and NDUFS6) key genes were screened via PPI and SVM-RFE analysis, respectively. These key genes displayed strong diagnostic efficacy for differentiating DR from DM in our in-house clinical cohort. Immune infiltration analysis revealed significant upregulation of activated mast cells, monocytes and M0 macrophages, along with downregulation of resting mast cells, in DR patients. Integrated CMap-based screening and molecular docking further proposed VU-0400193-3, Tyrphostin-AG-1295 and TG100-115 as candidate drugs against DR.</p><p><strong>Conclusions: </strong>This study provides novel insights into the circulating biomarkers for diagnosis of DR, and predicts therapeutic compounds for this disease.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147928963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in miRNAs profile in pregnant women with preeclampsia compared with healthy pregnant women.","authors":"Vorapong Phupong, Natthaya Chuaypen, Supawadee Mingmongkol, Patou Tantbirojn, Ruangsak Lertkhachonsuk","doi":"10.1186/s40246-026-00986-z","DOIUrl":"10.1186/s40246-026-00986-z","url":null,"abstract":"<p><p>Preeclampsia is a hypertensive and multisystemic disorder characterized by mild to severe hypertension during the second half of pregnancy. Circulating microribonucleic acids (miRNAs) have been identified as potential biomarkers for its diagnosis and prognosis. In this study, we compared global miRNA expression profiling in serum samples obtained from pregnant women belonging to three groups: women with severe preeclampsia pregnancies, mild preeclampsia pregnancies, and healthy pregnancies using the NanoString nCounter platform. We found that 26 miRNAs exhibited significant differential expressions between the three groups. Based on predefined selection criteria, miR-604 and miR-423-5p were initially identified as up-regulated, whereas miR-3615, miR-99b-5p, and miR-4443 were down-regulated by NanoString profiling. These candidate miRNAs were subsequently selected for qRT-PCR validation. qRT-PCR analysis confirmed that miR-99b-5p, miR-4443, and miR-604 were consistently down-regulated in both mild and severe preeclampsia compared with healthy pregnancies. miR-3615 demonstrated stage-dependent variation, with significant downregulation in mild preeclampsia and a relative increase in severe cases. Notably, only miR-423-5p exhibited the most pronounced dysregulation, showing slight reduction in mild preeclampsia but a marked up-regulation in severe preeclampsia, consistent with the NanoString results. These findings suggest that miR-423-5p may serve as a potential circulating biomarker associated with disease severity in preeclampsia.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147941280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Broad germline variant spectrum revealed by whole-exome sequencing in an underrepresented Latin American population with hereditary breast cancer.","authors":"Sarai Morales-González, Ricardo Fernández-Ramires, Hugo Carlos Bolzon Gonzalez, Alejandro E Sepúlveda-Perez, Ignacio A Silva-Mundaca, Lorena Seccia, Vinicius F Campos, Paulo Roberto Ferreira Júnior, Mateus José Dutra, Alexis Salas-Burgos, Guilherme Gischkow-Rucatti, Sebastián Morales-Pison","doi":"10.1186/s40246-026-00983-2","DOIUrl":"10.1186/s40246-026-00983-2","url":null,"abstract":"<p><strong>Background: </strong>Hereditary breast cancer (BC) accounts for a significant proportion of BC cases, yet germline variant interpretation remains limited in underrepresented populations such as those from Latin America. Most available genomic reference data derive from European and North American populations, constraining variant interpretations and clinical decision-making in other regions.</p><p><strong>Methods: </strong>We performed whole-exome sequencing in 140 Chilean patients with clinically suspected hereditary BC. Germline variants were analyzed across canonical BC predisposition genes recommended by current NCCN guidelines and an extended set of additional cancer susceptibility genes. Variants were annotated and manually classified following ACMG/AMP guidelines, incorporating ClinGen gene-disease validity resources and cancer-specific CanVIG consensus recommendations.</p><p><strong>Results: </strong>Expanded gene analysis resulted in an increased detection of pathogenic and likely pathogenic variants (~ 18% to ~ 24%) and reduced the proportion of patients with negative genetic results compared with canonical gene analysis alone. Pathogenic variants were most frequently identified in BRCA1 and BRCA2, followed by additional cancer susceptibility genes, with truncating variants representing the predominant alteration type. Exploratory analyses revealed a broad distribution of pathogenic variants across BRCA1 and BRCA2 gene regions.</p><p><strong>Conclusions: </strong>This study provides a comprehensive overview of the germline variant spectrum in Chilean patients with suspected hereditary BC and demonstrates the added value of extended gene analysis beyond canonical predisposition genes. These findings contribute to population-specific genomic data and support efforts to improve variant interpretation and equitable implementation of genomic medicine in underrepresented populations.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13435756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147941277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptome and plasma proteome analyses identify susceptibility genes and proteins for alcohol-related hepatocellular carcinoma.","authors":"Zhishuang Li, Menghan Liu, Jiacheng Li, Wuwei Li, Tingting Min, Runsan Pan, Wenqi Wang, Zhangrong Chen, Wei Li, Runze Huang","doi":"10.1186/s40246-026-00984-1","DOIUrl":"10.1186/s40246-026-00984-1","url":null,"abstract":"<p><strong>Background: </strong>Genome-wide association studies (GWAS) have identified loci associated with alcohol-related hepatocellular carcinoma (ALD-HCC); however, most risk variants lie in noncoding regions and the downstream regulatory architecture remains incompletely characterized. Integrating genetically predicted transcriptomic and circulating proteomic signals may facilitate target prioritization and biomarker discovery.</p><p><strong>Methods: </strong>An integrative analytic framework combining transcriptome-wide association study (TWAS), cross-tissue sparse canonical correlation analysis with the aggregate Cauchy association test (sCCA+ACAT), and plasma proteome-wide association study (PWAS) was applied to ALD-HCC GWAS summary statistics from 2,107 unrelated European individuals with alcohol-related liver disease (775 cases and 1,332 controls; 7,962,325 variants). Conditional and bivariate analyses were conducted to assess independence and potential shared cis-genetic regulation between transcriptomic and proteomic signals at risk loci. Colocalization analysis was further conducted to assess whether the identified signal pairs shared a causal genetic variant.</p><p><strong>Results: </strong>Fifteen previously unreported susceptibility genes were prioritized (11 by TWAS and 4 by sCCA+ACAT), and PWAS identified NCAN as a significant plasma protein-associated signal at an ALD-HCC risk locus. Conditional and bivariate analyses supported associations with genetically predicted expression of nine genes and genetically predicted plasma NCAN levels, indicating convergent transcript-protein signals within established risk regions. Through colocalization analysis in GWAS loci, we additionally identified 5 putative susceptibility genes.</p><p><strong>Conclusion: </strong>Integrative TWAS/sCCA+ACAT/PWAS analyses nominate candidate susceptibility genes and identify NCAN as a plausible circulating locus-level signal relevant to ALD-HCC risk, providing a genetic resource for further mechanistic investigation.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13344026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147928950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA-sequencing reveals cellular heterogeneity and identifies biomarkers for obstructive sleep apnea and migraine.","authors":"Qipeng Cen, Youfeng Xie, Wenyi Song, Tingting Cao, Qingyan Wei, Guining Liang, Lucong Liang, Chun Zou, Rongjie Li, Mika Pan, Li Su, Donghua Zou","doi":"10.1186/s40246-026-00981-4","DOIUrl":"10.1186/s40246-026-00981-4","url":null,"abstract":"<p><strong>Background: </strong>Obstructive sleep apnea (OSA), a prevalent sleep disorder associated with migraine, has unclear effects on cellular heterogeneity within this comorbid context.</p><p><strong>Results: </strong>A total of 75,502 cells from five cell types were identified from OSA and non-OSA samples (GSE214865), while 20,243 cells from four cell types were identified from migraine and healthy control samples (GSE269117). T cells were the most abundant immune cells in patients with OSA and migraine. HIF-1/NF-κB signaling had significant activity. FOS, FOSB, PDE3B, KLF6, RPS26, MTRNR2L8, MT-ATP8, PLCG2, and CCR7 were the key biomarkers of both OSA and migraine. A TCMNP software-based network was constructed with drug prediction revealed significant associations between Ma Huang and Bai Guo and their active components TCM00192 and TCM02096. Natural killer T cells were the least differentiated subtype and were inferred to be the starting point, closely connected to CD8⁺ T cells.</p><p><strong>Conclusion: </strong>Single-cell RNA analysis revealed a shared T cell-centered immune-dysregulated landscape in OSA and migraine, identifying common biomarkers and key pathways. These findings provide a crucial foundation for understanding comorbidities and developing new therapies.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13335133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147874126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-4788 promotes NSCLC progression by targeting DLG5 to enhance mitochondrial function.","authors":"Yanting You, Qifeng Peng, Xiaomei Chen, Meilin Chen, Jie Zhou, Baizhao Peng, Xiaohu Chen, Yanyan Liu, Qingfeng Du, Xiaoshan Zhao","doi":"10.1186/s40246-026-00968-1","DOIUrl":"10.1186/s40246-026-00968-1","url":null,"abstract":"<p><strong>Background/objectives: </strong>Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide. Although microRNAs (miRNAs) are known to play crucial roles in tumor progression, the biological function and mechanistic role of miR-4788 in NSCLC remain undefined. This study investigates the role and mechanism of miR-4788 in NSCLC proliferation and metastasis.</p><p><strong>Methods: </strong>miR-4788 expression and its prognostic significance were analyzed using The Cancer Genome Atlas (TCGA) data. In vitro assays were conducted in NSCLC cell lines transfected with miR-4788 mimics, DLG5 siRNA, or a 3'-UTR-truncated DLG5 overexpression plasmid. In vivo functional validation was performed in zebrafish and murine xenograft models. Functional assays included assessments of cell viability (CCK-8), proliferation (EdU incorporation, colony formation), cell cycle distribution, migration/invasion (wound healing, Transwell), and mitochondrial function (ATP, MMP, ROS, mitophagy markers). A dual-luciferase reporter assay was used to confirm DLG5 as a direct miR-4788 target, and rescue experiments were conducted to validate its downstream role.</p><p><strong>Results: </strong>miR-4788 was significantly upregulated in NSCLC tissues and was associated with a lower disease-specific survival rate. Its overexpression in vitro and in vivo promoted the proliferation, migration, and invasion of non-small cell lung cancer cells. This oncogenic effect was accompanied by enhanced mitochondrial function, evidenced by increased mitochondrial membrane potential, ATP production, and reactive oxygen species (ROS) levels, along with suppression of mitophagy (reduced Pink1/Parkin expression). Mechanistically, miR-4788 directly targets the 3'-UTR of DLG5, downregulating its expression, and restoring the function of DLG5 could alleviate the carcinogenic phenotype caused by miR-4788.</p><p><strong>Conclusions: </strong>miR-4788 functions as an oncogenic regulator in NSCLC, promoting tumor development by targeting DLG5 and promoting mitochondrial metabolic reprogramming. These findings provide new insights into the miR-4788-DLG5 axis in NSCLC and suggest its potential role in tumor metabolism and immune microenvironment remodeling.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147874077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severity-dependent risk of chromosomal abnormalities in fetuses with short long bones: a 10-year cohort study.","authors":"Yanlin Huang, Hongke Ding, Jian Lu, Ting Wang, Xiaomei Shi, Cuiqing Huang, Jing Wu","doi":"10.1186/s40246-026-00977-0","DOIUrl":"10.1186/s40246-026-00977-0","url":null,"abstract":"<p><strong>Background: </strong>Short long bones (SLBs) detected prenatally are associated with chromosomal abnormalities; however, risk stratification according to phenotypic severity and associated anomalies remains incompletely defined.</p><p><strong>Methods: </strong>In this 10-year retrospective cohort study (2015-2024), 790 fetuses with SLBs (≥ 2 SD below the gestational mean) underwent conventional karyotyping (CS) and/or chromosomal microarray analysis (CMA). SLBs were categorized by severity (mild, moderate, severe) and presentation (isolated vs. non-isolated). Detection rates were compared across subgroups.</p><p><strong>Results: </strong>Chromosomal abnormalities were identified in 38/790 fetuses (4.8%), including 2.2% numerical and 2.7% structural aberrations. The detection rate increased with limb shortening severity (3.1% in mild, 8.2% in moderate, and 8.8% in severe cases; P = 0.005). Non-isolated SLBs were associated with a significantly higher abnormality rate than isolated cases (7.7% vs. 2.2%, P < 0.001). CMA detected clinically relevant submicroscopic copy number variants missed by karyotyping, whereas karyotyping identified balanced rearrangements not detectable by CMA.</p><p><strong>Conclusions: </strong>Chromosomal abnormalities represent a measurable but limited proportion of fetuses with SLBs, with risk significantly influenced by phenotypic severity and coexisting anomalies. These findings support a risk-stratified framework for prenatal genetic evaluation and may inform clinical counseling and management strategies.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147868096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the prognostic role of senescence-related genes in gastric cancer through multi-omics integration and machine learning.","authors":"Yangkun Cao, Dongjie Li, Li Bao, Xiaoling Ding, Yongzhen Guo, Xiaobo Ni, Yang Liu","doi":"10.1186/s40246-026-00979-y","DOIUrl":"10.1186/s40246-026-00979-y","url":null,"abstract":"<p><p>Cellular senescence plays a context-dependent role in gastric cancer (GC), functioning both through tumor-suppressive arrest and the tumor-promoting senescence-associated secretory phenotype. However, its systematic integration into prognostic models remains limited. Here, we develop a novel interpretable framework to identify and validate a robust senescence-related gene signature for GC prognosis. We first introduce a dual-model interpretable feature selection strategy that integrates a biologically informed Kolmogorov-Arnold Network with a tabular foundation model to identify cancer-associated senescence genes. From the initial candidates, an ensemble of ten machine learning algorithms distills a core 4-gene signature to construct a Senescence Risk Score (SRS). The SRS proves to be a powerful and independent prognostic indicator, effectively stratifies patients into high- and low-risk groups with distinct overall survival across multiple cohorts. High-risk patients exhibit an \"immune-hot\" but potentially dysfunctional tumor microenvironment, characterized by enriched immune cell infiltration, elevated checkpoint expression, and distinct metabolic reprogramming favoring pathways such as angiogenesis and epithelial-mesenchymal transition (EMT). Furthermore, the SRS correlates with differential somatic mutation profiles and suggests potential sensitivity to specific chemotherapeutic agents. In vitro functional assays confirmed the oncogenic role of SERPINE1, a top-ranked core gene, in promoting GC cell proliferation. Regulatory network analysis revealed potential upstream transcription factors and miRNAs governing the signature. Collectively, we present a validated senescence-related prognostic signature that enables effective risk stratification of patients with gastric cancer.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}