Susceptibility genes, including single-nucleotide polymorphisms (SNPs) in the DNA sequences, genetically predispose certain individuals to developing adverse events (AEs) following vaccination. Such AEs are often undetected in initial clinical safety trials during vaccine licensing evaluations. Therefore, a comprehensive understanding of susceptibility genes is crucial for vaccine development, safety monitoring, and precision immunization. VaegenDB is a web-based centralized database and analysis system designed for managing, storing, and analyzing susceptibility genes associated with vaccine AEs. Basic information on these genes and supporting evidence are curated from peer-reviewed literature, while more detailed gene, AE, and vaccine data are automatically extracted from existing databases such as RefSeq and VIOLIN using in-house scripts. Currently, VaegenDB contains information on 160 susceptibility genes linked to 151 AEs and 86 vaccines. The system offers a user-friendly web interface that enables interactive querying and visualization of susceptibility genes. Bioinformatics analyses using VaegenDB reveal that a single susceptibility gene may harbor multiple genetic variations, one vaccine can be associated with several AEs, and a single AE may be influenced by multiple genes or SNPs. In addition, KEGG and GO enrichment analyses were employed to identify gene signatures—including functional annotations, mutation types, and expression patterns—associated with adverse reactions. The construction of this database and subsequent bioinformatics analyses help clarify enriched gene profiles and underlying mechanisms of vaccine-related AEs, thereby supporting rational vaccine design and advances in precision medicine.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12920-025-02292-4.

circSirt1 can ameliorate neointimal hyperplasia and provide protection against atherosclerosis. Single nucleotide polymorphisms (SNPs) in circRNA flanking introns, particularly within Alu elements, may alter back-splicing and influence circRNA formation efficiency. To investigate the association between polymorphisms in the circSirt1 flanking introns and susceptibility to myocardial infarction (MI), we performed a case-control study. This study included 541 coronary artery disease (CAD) cases and 278 controls. Four SNPs (including rs33957861, rs2273773, rs145758730, and rs34416841 in circSirt1 gene) genotyping was conducted utilizing the polymerase chain reaction-ligation detection reaction (PCR-LDR) technique. The associations of these SNPs with the susceptibility were analyzed using multivariate logistic regression, and the haplotype analysis was performed using SHEsis software. The data showed the C allele of rs34416841 was significantly associated with an increased risk of MI (adjusted OR = 1.65, 95% CI = 1.07-2.56, P = 0.024). Consistent trends were observed in co-dominant (OR = 1.70, 95% CI = 1.04-2.77, P = 0.034) and dominant models (OR = 1.73, 95% CI = 1.07-2.79, P = 0.025). Notably, the C allele of rs34416841 specifically increased progression risk from stable CAD to MI (OR = 1.62, 95%CI:1.09-2.42, P = 0.018). Stratified analyses demonstrated stronger associations among younger individuals (≤ 60 years), males, smokers, non-drinkers and hypertension subjects. Consistent with these results, the C-T-C-G haplotype containing rs34416841C allele was also associated with increased MI risk (OR = 1.43, 95% CI = 1.03-2.00, P = 0.035). However, no statistically significant association was observed between the rs34416841 polymorphism and CAD risk across all tested genetic models. The rs34416841 polymorphism, located within an Alu element in the flanking intron of circSirt1, demonstrates significant associations with both MI susceptibility and CAD progression in the Han Chinese population.

ObjectiveIntegrin alpha-3 (ITGA3) has been implicated in tumor metastasis in various cancers, but its role in epithelial ovarian cancer (EOC)-associated liver metastasis (LM) remains unclear. This study aimed to investigate its role in LM in primary EOC patients.MethodsIt was a retrospective study with a sample size of n = 235 receiving surgical resection at Puren Hospital Affiliated to Wuhan University of Science and Technology between January 2020 and December 2021, including 98 LM (LM group) and 137 non-LM cases (N-LM group). ITGA3 expression was assessed by immunohistochemistry. ROC curves were used for predictive performance analysis, Kaplan-Meier curves for survival analysis, and Cox regression analysis for identification of risk factors.ResultsMarkedly elevated ITGA3 expression in tumor tissues was found in the LM group (P < 0.001), which demonstrated strong predictive value for LM in EOC patients (area under the curve (AUC) = 0.881, sensitivity = 70.41%, specificity = 87.59%, P < 0.001), and strongly correlated with tumor size and postoperative residual lesions (both P < 0.05). Compared with the L-ITGA3 group, the H-ITGA3 group had a higher incidence of postoperative LM (P < 0.001) and showed a left-shifted curve in Kaplan-Meier analysis (P < 0.001). ITGA3 expression in tumor tissues (HR = 5.977), tumor grade (HR = 1.441), and postoperative residual lesions (HR = 1.697) were identified as independent risk factors for postoperative LM.ConclusionsITGA3 expression in tumor tissue significantly aids in predicting LM in EOC patients and is independently and closely related to adverse clinicopathological outcomes.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12920-025-02268-4.

ObjectiveThis study is conducted to investigate whether serum microRNA (miR)-141-3p can serve as a biomarker for early-stage diagnosis of endometriosis.MethodsA total of 246 patients who underwent laparoscopic examination and were diagnosed with endometriosis at our hospital between October 2020 and October 2022 were retrospectively enrolled as the Endometriosis group. This group was further allocated into Early-Endometriosis (Stage I-II) and Severe-Endometriosis (Stage III-IV) groups. Additionally, 87 healthy women with normal clinical parameters during the same period were selected as the control group. miR-141-3p expression in the serum of endometriosis patients were detected using RT-qPCR. The relationship of serum miR-141-3p expression with EHP-30 score in endometriosis patients was examined using Spearman. The diagnostic value of serum miR-141-3p for endometriosis was assessed by ROC analysis. Further ROC analysis was conducted to evaluate the diagnostic value of combined serum miR-141-3p and CA125 levels for early-stage endometriosis.ResultsSerum miR-141-3p expression was significantly lower in endometriosis patients and was negatively correlated with clinical staging. Serum miR-141-3p demonstrated excellent diagnostic performance for endometriosis (AUC = 0.916) and retained a high diagnostic value for early-stage endometriosis (AUC = 0.858). The diagnostic efficacy was further improved when combined with CA125 (AUC = 0.985).ConclusionSerum miR-141-3p expression decreases with disease progression in endometriosis patients and shows high clinical utility for the early-stage diagnosis of endometriosis. miR-141-3p expression may serve as a potential marker for diagnosis of endometriosis.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12920-025-02238-w.

Exome and genome sequencing have greatly improved the diagnosis of rare genetic disorders but remain limited in their ability to identify and classify non-coding variants, including intronic variants, cryptic splice-site alterations, and disruptions in regulatory regions. RNA sequencing (RNA-seq) has emerged as a powerful tool to bridge this gap by providing functional insights into genomic variants that disrupt splicing or gene expression, thereby aiding in variant interpretation and classification. We retrospectively reviewed 30 cases from the Utah Penelope Program and the Undiagnosed Diseases Network over a three-year period, in which RNA-seq was performed on whole blood and/or fibroblasts following either negative DNA sequencing or the identification of candidate variants requiring functional assessment. In these cases, RNA-seq identified exon skipping, cryptic splice-site activation, and intron retention, leading to transcript disruption. Additionally, positional enrichment analysis clarified X-inactivation patterns and dosage effects, confirming the pathogenicity of copy number variants. By detecting these transcript-level alterations, RNA-seq provided functional evidence supporting the reclassification of multiple variants of uncertain significance, contributing to diagnostic resolution in selected cases. This study underscores the clinical utility of RNA-seq in detecting splicing and regulatory defects that DNA sequencing and predictive tools alone cannot resolve. Integrating RNA-seq into clinical workflows can support variant classification, aid in diagnostic resolution for selected cases, and provide mechanistic insights into genetic disorders, contributing to patient care and genetic counseling.

BackgroundStomach adenocarcinoma (STAD) poses a major public health challenge across various populations, necessitating the construction of robust models for prognostic prediction and effective clinical therapies. Dysregulation of lactylation, a key regulatory mechanism in cell metabolism and gene expression, can either impede or promote tumor growth and metastasis.MethodsThis study got into the bottom of TCGA-STAD-sourced transcriptome data to profile lactylation-related genes and construct a gene signature through LASSO regression. A nomogram was further created to assess the prognostic performance of this model. Our investigation primarily concentrated on the expression of Dehydrogenase/reductase 7 (DHRS7) in STAD, with the verification of its correlations with clinical characteristics, immune cell infiltration, and cellular signaling pathways.ResultsDHRS7 expressed lower in STAD tissues, and that modulating DHRS7 levels could either promote or inhibit malignant behaviors associated with STAD. In the later stages of tumor progression, DHRS7 appeared to facilitate tumor growth through mechanisms such as immune evasion and activation of PI3K/AKT/mTOR signaling pathways, ultimately contributing to an unfavorable prognosis.ConclusionsDHRS7 has the potential to shift from acting as a tumor suppressor to functioning as an oncogene in modified TMEs, despite its lower expression levels in STAD tissues relative to normal tissues. This transformation accounts for the association between high DHRS7 expression in the later stages of STAD and a negative prognosis.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12920-025-02244-y.

Humans are exposed to ionizing radiation (IR), which causes direct and indirect DNA damage. Biodosimetry is a critical component of clinical care following radiation exposure, enabling accurate assessment and mitigation of health effects. The present study was conducted to investigate the ex vivo expression of the genes TNFRSF10B, ZMAT3, PLK2, and POLH in human peripheral blood samples exposed to X-radiation at doses of 0, 0.5, 2, and 4 Gy at 0, 4, 24, and 48 hours post-exposure. Investigating gene expression dynamics through biodosimetry is a novel approach that may provide insights into gene-specific responses, potentially enhancing the accuracy and sensitivity of radiation dose assessment. Peripheral blood samples were collected from five healthy volunteers and exposed to 0, 0.5, 2, or 4 Gy radiation with a 6 MV linear accelerator. Following the extraction of RNA and cDNA synthesis, gene expression analysis via qRT‒PCR was performed. These genes were normalized against the housekeeping gene β-actin, and the ΔΔCt method was used for statistical analysis of gene expression. The data were subjected to statistical analysis, and the level of significance (p < 0.05) was determined to test the effects of dose and time on gene expression. The expression of the TNFRSF10B, ZMAT3, POLH, and PLK2 genes was markedly dose- and time-dependent in response to X-ray radiation in vitro. Whole-blood samples irradiated at doses of 0, 0.5, 2, and 4 Gy and analyzed at four time points, 0, 4, 24, and 48 hours, respectively, revealed marked changes in the expression levels of the genes studied, revealing the mechanisms of the response at the cellular level to ionizing radiation. Although minor inter-individual variation in gene expression was observed, it did not significantly affect the overall trends, and the results remained statistically robust. These findings highlight a robust biodosimetry framework: TNFRSF10B demonstrated the highest diagnostic performance (AUC = 0.94; sensitivity = 98%; specificity = 75%; cut-off = 1.11), making it a highly reliable biomarker for radiation exposure. PLK2 also exhibited strong discriminative capacity (AUC = 0.84; sensitivity = 90%; specificity = 80%; cut-off =2.5), particularly for minimizing false positives. ZMAT3 (AUC = 0.78; sensitivity/specificity = 75%; cut-off = 3.21) showed balanced early-phase performance, whilePOLH (AUC = 0.73; sensitivity = 80%; specificity = 60%; cut-off = 1.10) may serve as a complementary marker. Collectively, these findings support a multi-gene expression approach for accurate biodosimetric assessment and improved triage following radiation exposure.

BackgroundThe intrapatient variability (IPV) of tacrolimus (Tac) has gradually become a new index for the prognosis of organ transplantation. The gene polymorphism is involved in the pharmacokinetic process of Tac. The aim of this study was to investigate the effects of genetic polymorphisms on Tac IPV and other clinical outcomes in heart transplant recipients during the early post-transplantation period.MethodsOur study retrospectively collected the clinical data and genotyping results of 48 heart transplant recipients. SPSS (21.0) and Graphpad Prism (8.0) were used to analyze the effect of gene polymorphism on Tac concentration (C0) and clinical outcome.Results The CYP3A5 rs15524 AA genotype has a higher trough concentrations/dose (C0/D) value than G allele carriers, and CYP3A7 rs776744 CC genotype has a higher C0/D value than T allele carriers. Patients with The CYP3A5 rs15524 and CYP3A7 rs776744 mutants had a higher IPV. One year after heart transplantation, the mortality of wild-type and mutant CYP3A5 rs15524 patients due to rejection was 0 vs. 10.7% (P = 0.255). The mortality caused by rejection in wild-type patients and mutant patients of CYP3A7 rs776744 was 4.5% vs. 7.7% (p = 0.564).ConclusionsGenetic polymorphisms of CYP3A5 rs15524 and CYP3A7 rs776744 affect tacrolimus metabolism in heart transplant recipients, significantly affecting Tac C0/D during the early postoperative period. In addition, gene polymorphism may be related to Tac IPV and clinical outcome in patients with early heart transplantation.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12920-025-02231-3.

Glioblastoma (GBM), the most malignant central nervous system cancer, has a median survival rate of 14–16 months. GBM patients have a poor prognosis despite rigorous multi-modal treatments like surgical resection, chemotherapy, and radiation. A systematic bioinformatics analysis of GXA gene expression datasets showed thirty-three overexpressed genes in GBM that were enriched in neuroactive ligand receptor interaction. Subsequently, bulk brain tissue gene expression profiling showed high to moderate expression of CCK, VGF, APLN, CNR1, GRIA4, and PDYN in the cortex, frontal cortex-BA9, BA24 region, cerebellar hemisphere, cerebellum, hippocampus, amygdala, basal ganglia, hypothalamus, substantia nigra, and spinal cord. Interesting, the cortex, frontal cortex-BA9, and BA24 regions had unbelievably high CCK expression. Brain cortex and frontal lobe mutational scoring showed significant rates of IDH1 (49%), TERT (25%), SETD2 (17%), and BRAF (9%). We initially confirmed glioblastoma (GBM) malignancy and therapeutic responses to CCK overexpression and IDH1 mutations in cerebral cortex and frontal cortex tissue samples. However, Mann–Whitney analysis revealed ZBTB20 mutations cause CCK expression, not IDH1 mutations. Overall, CCK expression and ZBTB20 mutations may be used in therapeutic treatments as predictive and diagnostic markers. The expression of CCK was not linked with overall survival and excludes its potential application as prognostic biomarker for GBM. This study showed that CCK and ZBTB20 based predictive and diagnostic technologies can improve precision and personalization of targeted cancer therapies for GBM patients. Nevertheless, experimental evidences have yet to reveal additional therapeutically meaningful connections between CCK expression and ZBTB20 mutations.