BMC Medical Genomics最新文献

{"title":"A case report of a family with MYH9 gene mutation-related disease in an ethnic minority group and literature review.","authors":"Xia Yan, Zhenzhen Li, Shaojun Huang, Xiaoxia Yang, Ming Chang, Zhengjiang Cheng, Lan-Ting Zhou","doi":"10.1186/s12920-026-02347-0","DOIUrl":"10.1186/s12920-026-02347-0","url":null,"abstract":"<p><p>BACKGROUND: May-Hegglin anomaly, a rare autosomal dominant disorder caused by MYH9 mutations, is characterized by the classic \"triad\" of thrombocytopenia, giant platelets, and granulocyte cytoplasmic inclusion bodies; some patients also present non-hematological symptoms. RESULTS: We reported a family of MYH9-related disease. The proband had microscopic hematuria, proteinuria, and thrombocytopenia on physical examination; blood smear re-examination showed giant platelets and Döhle-like bodies. His medical history included childhood epistaxis; his father had unexplained thrombocytopenia/proteinuria, and his younger brother had epistaxis/purpura/thrombocytopenia. Whole-exome sequencing (validated by Sanger sequencing) confirmed the diagnosis. CONCLUSIONS: Diagnosis of MYH9-related diseases depends on combined laboratory morphology and molecular biology. Routine blood tests and smear microscopy (identifying abnormal giant platelets/Döhle-like bodies) provide initial screening clues, while gene sequencing enables accurate diagnosis and pathogenesis clarification, forming a complete screening-to-confirmation diagnostic pathway. </p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel maternally inherited CDKN1C variant in a familial beckwith-wiedemann syndrome case: expanding the genotype-phenotype spectrum.","authors":"Shanshan Wu, Yanan Zhang, Huifeng Zhang, Xue Yan, Yalei Pi","doi":"10.1186/s12920-026-02351-4","DOIUrl":"10.1186/s12920-026-02351-4","url":null,"abstract":"<p><p>BACKGROUND: Cyclin-dependent kinase inhibitor 1 C (CDKN1C), encoding the p57KIP2 protein, serves as a critical negative regulator of cellular proliferation. Loss-of-function mutations in CDKN1C are responsible for 5–8% of sporadic and 40% of familial Beckwith-Wiedemann syndrome (BWS) cases, with 133 variants catalogued in the Human Gene Mutation Database (HGMD). We herein report a novel CDKN1C variant in a familial BWS case. A female neonate delivered preterm via cesarean section for severe preeclampsia manifested large for gestational age, macroglossia, omphalocele, and nevus flammeus. Immediate postnatal repair of the omphalocele was conducted. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) analysis of genomic DNA from peripheral blood demonstrated normal methylation at the 11p15.5 imprinting control region without copy number variations. Whole-exome sequencing (WES) showed no pathogenic variants, whereas whole-genome sequencing (WGS) detected a novel maternally inherited heterozygous frameshift variant in CDKN1C (NM_000076.2: c.617_635dup, p.Ala213GlyfsTer34). Longitudinal follow-up to age 4.5 years documented persistent postnatal overgrowth, with weight consistently tracking above the 97th percentile ( > + 2 SD). Motor, language, and cognitive development had gradually improved, progressing from mild delay to normal status. A transient leg length difference was initially noted but resolved on follow-up examination. The tumor marker alpha-fetoprotein (AFP) had normalized, and no tumors were detected during monitoring. CONCLUSION: This case reinforces the critical link between CDKN1C loss-of-function variants and abdominal wall defects. Our findings underscore the necessity of CDKN1C sequencing in Beckwith-Wiedemann spectrum (BWSp) diagnostics, particularly for fetuses presenting with omphalocele and negative 11p15 epigenetic testing. The identification of the novel NM_000076.2: c.617_635dup variant expands the genotype-phenotype landscape of BWS, facilitating more precise genetic counseling and subtype-specific management. </p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147519764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacogenomic study of the effects of saxagliptin on glucose control and hypoglycemic events.","authors":"Marc-Olivier Pilon, Simon de Denus, Géraldine Asselin, Marc-André Legault, Hervira Brenda Ngongang Kwandjang, Amina Barhdadi, Louis-Philippe Lemieux Perreault, Diane Valois, Ian Mongrain, Carolina Haefliger, Dirk S Paul, Ewan R Pearson, Jean-Claude Tardif, Marie-Pierre Dubé","doi":"10.1186/s12920-026-02348-z","DOIUrl":"10.1186/s12920-026-02348-z","url":null,"abstract":"<p><p>BACKGROUND: Saxagliptin is a DPP-4 inhibitor widely used to manage type 2 diabetes, though genetic contributors to variability in response remain unclear. This study aimed to identify genetic variants associated with the efficacy and safety of saxagliptin using genome-wide association studies (GWAS) with data from randomized controlled trials. METHODS: GWAS were conducted on glycated hemoglobin (HbA1c) levels and hypoglycemic events in saxagliptin-treated individuals from 12 phase II or III clinical trials. Additional exploratory traits included fasting glucose, weight, body mass index, systolic and diastolic blood pressure, heartbeat, and renal function. Primary analyses focused on participants of European ancestry, followed by analyses in the overall multi-ancestry cohort. Linear mixed models for continuous traits and Cox proportional hazards models for time-to-event analyses were used, including gene-by-sex and gene-by-treatment interactions. We also performed a transcriptome-wide association study (TWAS) to identify genes whose predicted expression is associated with the response to saxagliptin using the S-PrediXcan framework. RESULTS: Among 1 016 European and 1 826 multi-ancestry saxagliptin-treated participants, no genome-wide significant associations were observed. Suggestive associations included rs2168426:T > C near UBE2E1 for HbA1c (p = 1.0 × 10⁻⁷) and rs138558907:C > T near CCSER2 for hypoglycemia (p = 6.1 × 10⁻⁸). Treatment interaction analyses showed a stronger rs2168426 effect on HbA1c among saxagliptin users compared with non-users (pint = 9.2 × 10⁻³). The TWAS revealed three genes that significantly associated with HbA1c in human tissues: OGFOD3 in aorta (p = 8.3 × 10⁻⁷), TBC1D3D in coronary artery (p = 3.3 × 10⁻⁶), and TYSND1 in amygdala (p = 3.9 × 10⁻⁶). In the multi-ancestry cohort, KDM7A in whole blood was significantly associated with HbA1c (p = 3.6 × 10⁻⁶). CONCLUSION: Larger, diverse studies are needed to identify pharmacogenomic determinants of responses to saxagliptin. </p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenomics of multidrug-resistant Escherichia coli from bloodstream infections in South Africa.","authors":"Bakoena Ashton Hetsa, Esther Eyram Asare Yeboah, Arshad Ismail, Sabiha Yusuf Essack, Daniel Gyamfi Amoako","doi":"10.1186/s12920-026-02349-y","DOIUrl":"10.1186/s12920-026-02349-y","url":null,"abstract":"<p><p>BACKGROUND: Escherichia coli (E. coli) is a leading cause of bloodstream infections (BSIs) globally, with multidrug-resistant (MDR) strains complicating treatment outcomes. In South Africa, genomic data on such isolates remain scarce. To elucidate the genomic landscape of E. coli isolates from bloodstream infections (BSIs) collected over a one-year period in the uMgungundlovu District, South Africa, with a focus on the resistance and virulence genes, mobile genetic elements (MGEs), genetic synteny, sequence types (STs), and phylogenomic context. METHODS: Twenty-five non-duplicate E. coli isolates were recovered from blood cultures and subjected to antimicrobial susceptibility testing. All twelve MDR isolates underwent whole-genome sequencing and bioinformatic analysis. RESULTS: The MDR isolates comprised six distinct STs, notably high-risk international lineages ST131 (33.3%) and ST69 (25.0%), spanning five phylogroups, predominantly B2 and D. Eight O: H serotypes were identified, with O25:H4 and O45:H16 being most frequent. CH-typing revealed dominant CH types CH40-30 (ST131) and CH35-27 (ST69) and fimH alleles such as fimH30 and fimH27. The isolates encoded β-lactamases, including blaCTX-M-15, blaTEM-1B and blaOXA-1, frequently co-located with MGEs. Notably, blaCTX-M-15 was chromosomally integrated within a Tn3–ISEcp1 transposon unit, while blaTEM-1B and blaOXA-1 were associated with diverse plasmid-associated syntenic architectures flanked by IS1, IS91, or integron-associated regions. Other antibiotic resistance genes were detected, conferring resistance to aminoglycosides (aph(3’)-Ia, aac(3)-IIa, aac(3)-IIe, aadA1, aadA2), sulfonamides (sul1, sul2) and trimethoprim (dfrA variants). A diverse array of virulence genes was identified, associated with adhesion, iron acquisition, serum resistance, and toxin production. Phylogenomic clustering revealed close relationships between local ST131/ST69 isolates and counterparts across Africa. CONCLUSIONS: The study identifies diverse MDR E. coli clones circulating in bloodstream infections, notably high-risk lineages ST131, ST69 and ST10, with complex resistance and virulence gene arsenals facilitated by MGEs. These insights reinforce the imperative for genomic surveillance to guide infection control and antibiotic stewardship in high-burden settings. </p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The genetic landscape of breast cancer in young women from Morocco: implications for diagnosis and treatment.","authors":"Brahim El Hejjioui, Abdelhamid Bouramtane, Laila Bouguenouch, Badreddine Elmakhzen, Mohamed Ahakoud, Moulay Abdelilah Melhouf, Karim Ouldim, Sanae Bennis","doi":"10.1186/s12920-026-02343-4","DOIUrl":"10.1186/s12920-026-02343-4","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Mortality rates from breast cancer in young women have fallen considerably in high-income countries but continue to rise in low-income countries such as Morocco. Young women with breast cancer face unique challenges due to the aggressive nature of the disease, the presence of aggressive subtypes (e.g., triple-negative, HER2-positive, and luminal B), and limited access to timely diagnosis and treatment. In addition, genetic factors play crucial roles in patient prognosis and response to treatment. The molecular landscape of breast cancer in young women has important implications for personalized medicine, such as the use of targeted therapies, namely poly (ADP-ribose) polymerase (PARP) inhibitors, which are particularly effective in patients with BRCA gene mutations. However, research into the genetic landscape of breast cancer in young women from low-income regions is limited, and the potential of personalized medicine to improve outcomes remains underexplored.This study aims to analyze the genetic landscape of breast cancer in young Moroccan women, with a focus on genetic alterations beyond the BRCA1 and BRCA2 genes. By expanding the panel of genes, we hope to identify other genetic variants that may influence the diagnosis, treatment, and follow-up of this high-risk population.Methods A retrospective study was conducted on 60 young women who were diagnosed with breast cancer between 2019 and 2024 at Hassan II University Hospital, Fez, Morocco. Genetic analysis was performed via next-generation sequencing (NGS) technology, specifically the Ion S5 sequencer and a custom-designed gene panel targeting 28 key genes associated with breast cancer and hereditary cancer syndromes.For statistical analysis, descriptive statistics were calculated for clinical variables (e.g., age, grades, molecular subtypes, genetic mutations). The correlation between genetic mutations and clinical outcomes was assessed using chi-square tests. All statistical analyses were performed using SPSS software. A significant level of p &lt; 0.05 was used for all tests.Results The cohort had a mean age of 34.6 years, with 36.7% reporting a family history of cancer. DNA sequencing of the 60 patients yielded 15 pathogenic variants and 3 likely pathogenic variants; the genes involved being BRCA1, BRCA2, and ATM for the pathogenic variants, whereas for the likely pathogenic variants, the genes involved were MUTYH and APC, which suggests the presence of other potential genetic risk factors other than the BRCA1 and BRCA2 genes. Furthermore, the BRCA1 gene was mutated in 45% of patients with triple-negative breast cancer, highlighting the important role of genetic testing in identifying high-risk patients, which should greatly improve the management and treatment of the disease.Conclusion This study highlights the importance of genetic testing for personalized treatment of young breast cancer patients. Firstly, these results will help us to improve outcomes for young women with aggress","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147479660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From gene to heart: the impact of a novel SGCD variant in familial dilated cardiomyopathy.","authors":"Samira Kalayinia, Amirhossein Poopak, Mahdieh Soveizi, Majid Maleki","doi":"10.1186/s12920-026-02342-5","DOIUrl":"10.1186/s12920-026-02342-5","url":null,"abstract":"<p><p>BACKGROUND: Dilated cardiomyopathy (DCM) is a leading cause of heart failure, often resulting in reduced ejection fraction and progressive cardiac dysfunction. Although up to half of idiopathic DCM can be linked to genetic variants, many familial cases still lack a definitive molecular diagnosis. Sarcoglycan delta (SGCD) encodes a crucial component of the dystrophin-glycoprotein complex, and variants in this gene have been implicated in both muscular dystrophies and cardiomyopathies. METHODS: We evaluated a three-year-old girl presenting with a confirmed diagnosis of DCM. Clinical assessments included echocardiography and cardiac magnetic resonance imaging (CMR), revealing moderate-to-severe systolic and diastolic dysfunction. Whole exome sequencing (WES) was performed to investigate potential causative variants. In silico analysis and Sanger sequencing were used to confirm and characterize any identified alteration in the proband and her parents. RESULTS: WES identified a novel heterozygous SGCD variant, NM_000337.6(SGCD): c.647 A > T, p.(Asn216Ile), located in exon 8. Sanger sequencing confirmed this variant’s presence in the proband and her father, suggesting a familial inheritance pattern. In silico predictive tools supported a likely deleterious effect of the variant,, with functional analysis indicating possible disruption of δ-Sarcoglycan’s structure. This variant was absent in public variant databases, underscoring its rarity. Comparative evaluation of known SGCD variants further highlighted exon 8 as a possible mutational hotspot in DCM. CONCLUSION: These findings expand the variant spectrum of SGCD and reinforce its role in familial DCM. Genetic screening for SGCD variants in individuals with idiopathic or familial cardiomyopathy can improve early diagnosis, guide targeted interventions, and inform genetic counseling. Our results underscore the clinical importance of integrating molecular diagnostics to enhance personalized management of DCM. </p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13112781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147466719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the temporal dynamics of radiation-induced lung injury: a multi-omics integration of transcriptomic, proteomic, and metabolic reprogramming.","authors":"Dabin Wu, Fei Tang, Yixin Zhang, Xiaoyue Zhang, Yuan Peng, Yu Hou, Zhenzhou Yang, Zaicheng Xu","doi":"10.1186/s12920-026-02345-2","DOIUrl":"10.1186/s12920-026-02345-2","url":null,"abstract":"<p><p>Radiation-induced lung injury (RILI) arises from the unavoidable exposure of normal lung tissue during radiotherapy for thoracic malignancies. It remains a dose-limiting complication in thoracic radiotherapy, critically impacting treatment efficacy and long-term patient survival. Despite its clinical significance, the dynamic molecular reprogramming underlying RILI progression remains poorly characterized. Utilizing a C57BL/6J thoracic irradiation mouse model validated by histopathological analysis, we implemented an integrative tri-omics approach (RNA-seq, LC-MS/MS proteomics, and UHPLC-QTOF metabolomics) to systematically map the temporal evolution of RILI at critical phases: acute inflammation, transitional, and fibrotic. The three periods correspond to 4 weeks, 8 weeks, and 16 weeks after the mice received 16 Gy of electron beam irradiation to the thoracic region. Combined analysis using complete-linkage hierarchical clustering revealed co-expression modules, and Ces2e was identified as a pivotal node exhibiting sustained upregulation at both transcriptional and translational levels during early pathogenesis. Functional enrichment revealed time-dependent activation of xenobiotic metabolism and extracellular matrix (ECM)-receptor interaction pathways, with Ces2e overexpression correlating with macrophage polarization and lipid peroxidation accumulation. This temporal multi-omics atlas not only deciphers stage-specific molecular signatures of RILI but also nominates Ces2e as a candidate early-stage molecular marker.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13093917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147430564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shared molecular signatures between atrial fibrillation and chronic obstructive pulmonary disease: an integrated bioinformatic analysis with experimental validation.","authors":"Wei Zhou, Qian Tang, Dandan Chen, Jiulin Chen, Linyan Shi, Fuliang Luo, Fei Yan, Yifan Mao, Huimin Lu, Xing Zhou, Zhangrong Chen, Wei Li","doi":"10.1186/s12920-026-02335-4","DOIUrl":"10.1186/s12920-026-02335-4","url":null,"abstract":"<p><p>BACKGROUND: Atrial fibrillation (AF) and chronic obstructive pulmonary disease (COPD) are highly prevalent conditions that significantly impact patient outcomes. While mounting evidence suggests a strong epidemiological and clinical association between AF and COPD, the molecular basis underlying their frequent co-occurrence remains incompletely characterized. Rather than inferring direct disease-specific mechanistic links, this study aimed to identify shared systemic inflammatory and immune-related transcriptional signatures that are detectable across different tissues in AF and COPD. RESULTS: A total of 208 DEGs were found to be shared between AF and COPD. Functional enrichment analyses indicated that these genes were predominantly associated with inflammatory, immune, and extracellular matrix–related biological processes, including the NOD-like receptor, Influenza A, Phospholipase D, and ECM-receptor interaction pathways. PPI network analysis and external dataset verification highlighted CASP1, CXCR2, and IFIT5 as reproducibly upregulated genes across independent AF and COPD transcriptomic datasets. Their elevated expression was further observed in AF, COPD, and comorbid samples in exploratory validation experiments. No single TF or miRNA was found to simultaneously regulate all three genes, suggesting heterogeneous and context-dependent regulatory patterns rather than a unified regulatory axis. Drug–gene association analysis identified estradiol and methyl methanesulfonate as compounds computationally linked to the shared gene set, without implying biological efficacy or therapeutic applicability. CONCLUSION: This study delineates shared inflammatory and immune-related transcriptional signatures observed across AF and COPD datasets, highlighting common pathways and candidate genes that may reflect systemic inflammatory states. These findings are hypothesis-generating and primarily reflect shared systemic inflammatory and immune responses rather than disease-specific causal mechanisms, providing a bioinformatic framework for future mechanistic and clinical investigations. </p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13094198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147430545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular senescence in gastric cancer: a novel prognostic stratification and immune predictor.","authors":"Cheng-Zhi Wei, Yu-Ting Li, Zhi-Hao Lin, Fei-Zhi Lin, Xiao-Jiang Chen, Run-Cong Nie, Guo-Ming Chen, Zhi-Cheng Xue, Zi-Qi Zheng","doi":"10.1186/s12920-026-02346-1","DOIUrl":"10.1186/s12920-026-02346-1","url":null,"abstract":"<p><p>Cellular senescence, a state of permanent arrest of the cell cycle in response to various damage, exerts dual impact on tumor initiation and progression and has emerged as a promising therapeutic target. However, an applicable tool to quantify senescence remains exclusive. In this study, we investigated the role of senescence in gastric cancer (GC) progression through the analysis of TCGA-STAD cohort. According to senescence-associated gene (SAG) expression signatures, TCGA-STAD was divided into distinct senescence clusters. Cluster B with elevated expression of SAGs was associated with a poorer prognosis and a tumor microenvironment that was more conducive for tumor growth. Based on prognosis-associated differentially expressed genes (DEGs) between senescence clusters, we constructed cellular senescence score system (SSS) to quantify senescence of GC. SSS could serve as an independent prognostic factor and, notably, has the potential to identify patients who may benefit from immunotherapy. This indicates the strong potential of SSS as a biomarker for predicting immunotherapeutic response. In conclusion, SSS provides a reliable tool for prognosis prediction and treatment strategies for GC patients.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13094389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147430600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apolipoprotein D downregulation in OSCC: multi-database validation and clinical significance.","authors":"Shuting Wang, Jun Zhao, Rui Bai, Jianbo Ou, Chan Tang, Jiayi Hang, Xiaolin Nong","doi":"10.1186/s12920-025-02190-9","DOIUrl":"10.1186/s12920-025-02190-9","url":null,"abstract":"<p><strong>Background: </strong>Apolipoprotein D (APOD), a member of the lipocalin superfamily, plays a pivotal role in apoptosis, cancer, immune responses, and neural injury repair. Its association with various cancer types has been well-documented, but its expression and clinical implications in oral squamous cell carcinoma (OSCC) remain underexplored. Our study aims to investigate the expression and clinical significance of APOD in OSCC.</p><p><strong>Methods: </strong>A comprehensive analysis of APOD mRNA and protein expression in OSCC was conducted using multi-omics data from TCGA, GEO, and CPTAC databases. The findings were validated through qRT-PCR and immunohistochemistry (IHC) on OSCC tissue samples. Diagnostic and prognostic potential of APOD was assessed using summary receiver operating characteristic (sROC) curves and Kaplan-Meier survival analysis. Multivariate Cox regression analysis was performed to adjust for confounding factors and identify independent prognostic markers for survival. Gene set enrichment analysis (GSEA) was used to explore the signaling pathways associated with APOD and their biological relevance. Ethical approval for research involving human subjects was obtained from an ethics committee.</p><p><strong>Results: </strong>Analysis of public databases revealed significant downregulation of both APOD mRNA and protein in OSCC tissues compared to normal mucosal controls. Results from clinical samples corroborated these findings. The sROC analysis indicated that APOD may serve as a promising diagnostic biomarker for OSCC. Multivariate Cox regression analysis identified pathological T stage as an independent prognostic factor, independent of clinical T stage and lymphovascular invasion, while APOD, although associated with prognosis, was not a robust predictor. GSEA highlighted a strong positive correlation between APOD expression and key components of Type I interferon signaling (JAK1, TYK2, STAT2), suggesting that APOD downregulation may contribute to OSCC progression by inhibiting the Type I interferon-JAK-STAT pathway.</p><p><strong>Conclusion: </strong>APOD expression is significantly reduced in OSCC, demonstrating potential as a diagnostic and prognostic biomarker. Its downregulation may facilitate disease progression through disruption of the Type I interferon-mediated JAK-STAT signaling pathway.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13107711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147430464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}