Genes & genomics最新文献

{"title":"Multi-omics profiling uncovers LINC00486-associated lncRNA regulation in human traumatic brain injury.","authors":"Tala Al-Rubaye, Zenab Isa, Doga Erenkol, Elham Tarahomi, Nuray Sogunmez Erdogan","doi":"10.1007/s13258-025-01687-y","DOIUrl":"https://doi.org/10.1007/s13258-025-01687-y","url":null,"abstract":"<p><strong>Background: </strong>Traumatic brain injury (TBI) induces broad molecular changes in the human brain, altering gene expression in diverse neural and glial cells. While the transcriptional effects of TBI on protein-coding genes are well characterized, the roles of long noncoding RNAs (lncRNAs), key regulators of gene expression and chromatin, remain largely unknown.</p><p><strong>Objective: </strong>Our objective was to identify lncRNAs altered in TBI and explore their potential regulatory functions.</p><p><strong>Methods: </strong>We applied an integrative multi-omics approach combining single-nucleus RNA sequencing (snRNA-seq), isoform-level transcriptomics, transposable element (TE) annotation, and RNA-binding protein (RBP) interaction analyses. Public snRNA-seq datasets from cortical tissues of 12 TBI patients and 5 controls were analyzed to resolve injury-driven transcriptional signatures. We have performed differential expression analysis on 12,801 human lncRNAs, examined isoform-specific expression with TE content, and explored RBP-lncRNA interactions using CLIP-seq data.</p><p><strong>Results: </strong>Cell-type diversity decreased in TBI, and reactive and progenitor-like states were expanded. We identified 190 upregulated lncRNAs, mainly in glial cells. Among these, LINC00486 emerged as a brain-enriched lncRNA consistently increased after TBI. Isoform analysis showed its dominant brain isoform contains LINEs and LTRs, linking it to regulatory networks associated with endogenous retroelement activation. Functional enrichment connected LINC00486 to neurodevelopment, serotonin metabolism, and neuroinflammatory pathways. CLIP-seq data confirmed its interactions with stress-responsive RBPs such as AGO2 and TARDBP.</p><p><strong>Conclusions: </strong>Our multi-omics analysis identifies LINC00486 as a potential regulator of transcriptional plasticity in TBI. Its TE content and RBP interactions suggest a role in lncRNA-mediated regulatory networks during injury, highlighting possible therapeutic targets in neurotrauma.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PSM-SMOTE: propensity score matching and synthetic minority oversampling for handling unbalanced microbiome data.","authors":"Jeongsup Moon, Zhe Liu, Taesung Park","doi":"10.1007/s13258-025-01688-x","DOIUrl":"https://doi.org/10.1007/s13258-025-01688-x","url":null,"abstract":"<p><strong>Background: </strong>Predictive models using microbiome data often suffer from covariate imbalance and class imbalance, biasing results. Propensity Score Matching (PSM) balances covariates but reduces sample size, while borderline synthetic minority oversampling technique (borderline-SMOTE) oversamples minority classes but can generate uninformative examples.</p><p><strong>Objective: </strong>To develop and evaluate PSM-SMOTE, a novel hybrid sampling method that integrates PSM and borderline-SMOTE to handle both covariate and class imbalance in microbiome data.</p><p><strong>Methods: </strong>We developed PSM-SMOTE, a three-step hybrid sampling algorithm for microbiome data: (1) PSM at four caliper levels to balance covariates, (2) selection of at least ten robust differential markers via seven statistical tests with false discovery rate correction, and (3) application of borderline-SMOTE on the marker-based distance matrix to oversample minority classes. We evaluated PSM-SMOTE on three publicly available microbiome case-control datasets: pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC), and obesity, using logistic regression (LR), random forest (RF), and support vector machine (SVM) classifiers. Performance was assessed via area under the ROC curve (AUC).</p><p><strong>Results: </strong>PSM-SMOTE improved test AUCs in multiple model-dataset combinations compared with using PSM alone. Notably, for the RF model, PSM-SMOTE consistently enhanced AUC across nearly all oversampling settings in the PDAC and obesity cohorts. For the SVM model, PSM-SMOTE also achieved a significant AUC increase in the CRC cohort. For the LR model, PSM-SMOTE showed modest improvement under strict matching.</p><p><strong>Conclusion: </strong>PSM-SMOTE effectively addresses dual imbalance in microbiome data and consistently enhances performance, providing a practical solution for imbalanced data analyses.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A prognostic model for basal-like breast cancer based on beta-alanine metabolism genes: EHHADH as a potential biomarker and target for drug screening.","authors":"Xianjie Cheng, Birong Liu, Hong Lou, Fei Guo, Qiangsheng Xiao","doi":"10.1007/s13258-025-01674-3","DOIUrl":"https://doi.org/10.1007/s13258-025-01674-3","url":null,"abstract":"<p><strong>Background: </strong>The high heterogeneity of basal-like breast cancer (BLBC) impedes early diagnosis and accurate prognosis. Beta-alanine, a non-essential amino acid involved in various metabolic pathways, accumulates in BLBC cells and may exacerbate tumor progression.</p><p><strong>Objective: </strong>This study aimed to develop a prognostic model based on beta-alanine metabolism genes and investigate the clinical significance and therapeutic potential of EHHADH in BLBC.</p><p><strong>Methods: </strong>We applied Least Absolute Shrinkage and Selection Operator regression to 22 beta-alanine metabolism genes to construct a prognostic model using transcriptomic data. Subsequent analyses included overall survival, mutation landscape, functional enrichment, drug sensitivity, and in vitro validation of EHHADH function. Structure-based virtual screening was conducted to identify potential EHHADH inhibitors.</p><p><strong>Results: </strong>A beta-alanine metabolism-related prognostic signature was successfully developed. EHHADH was identified as a risk gene negatively associated with survival. High EHHADH expression correlated with increased sensitivity to chemotherapeutic agents, including docetaxel, doxorubicin, gemcitabine, paclitaxel, tamoxifen, and vinorelbine. Knockdown of EHHADH reduced BLBC cell proliferation and migration. Virtual screening revealed several candidate small molecules targeting EHHADH.</p><p><strong>Conclusion: </strong>This study establishes a prognostic model based on beta-alanine metabolism in BLBC and identifies EHHADH as a potential biomarker and drug target, providing insights for precision therapy in metabolically reprogrammed breast cancer.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assembly of a high-quality Polypterus senegalus diploid genome.","authors":"Jeong Woen Shin, Bo-Mi Kim, Jun Kim, Jae-Sung Rhee","doi":"10.1007/s13258-025-01685-0","DOIUrl":"https://doi.org/10.1007/s13258-025-01685-0","url":null,"abstract":"<p><strong>Background: </strong>Polypterus senegalus is a major actinopterygian fish that provides vital insights into vertebrate terrestrial adaptation. Advances in sequencing technologies have enabled improvements to the reference genome of P. senegalus, highlighting the need to expand research on this species.</p><p><strong>Objective: </strong>In this study, we sought to construct high-quality, partially-phased, assemblies of the P. senegalus genome using high-fidelity long-read sequencing data.</p><p><strong>Methods: </strong>First, partially-phased assemblies of P. senegalus genome using PacBio HiFi data. And then, our assemblies were compared with a previously published genome in terms of total length, contiguity, base-level accuracy, and Benchmarking Universal Single-Copy Orthologs (BUSCO) completeness, including resolution of repetitive regions and identification of telomere-telomere chromosomes.</p><p><strong>Results: </strong>Compared with a previously published genome, our assemblies exhibit improved quality in overall quality. A total of 20,940 genes were annotated employing integrated short-read and long-read RNA sequencing data. Transcriptomics revealed the gene-expression relationships between 12 tissue types and the distinct expression patterns of genes associated with key evolutionary traits, such as aerial respiration, angiogenesis, and limb flexibility. Notably, several genes including Tcf21, Foxf1, and Tbx3a were coordinately expressed in the lungs and swim bladder, supporting shared origins and developmental patterns. Analyses of the correlations among tissues revealed physiological similarities between the lungs, kidneys, and spleen.</p><p><strong>Conclusion: </strong>Our results provide a valuable genomic resource for P. senegalus and offer novel insights into the molecular basis of vertebrate organ evolution and adaptation.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging technologies and clinical translation of urine-based liquid biopsy in urological cancers.","authors":"Seo-Yeong Yoon, Gi-Eun Yang, Jong-Kil Nam, Hyeok-Jun Goh, Tae-Nam Kim, Sun-Hee Leem","doi":"10.1007/s13258-025-01680-5","DOIUrl":"https://doi.org/10.1007/s13258-025-01680-5","url":null,"abstract":"<p><p>Urine-based liquid biopsy represents a transformative, non-invasive diagnostic approach that enables the molecular profiling of tumor-derived biomarkers shed into the urinary tract. By overcoming the limitations of traditional tissue biopsies, this methodology facilitates early cancer detection, real-time monitoring of therapeutic response, and longitudinal disease surveillance. This review provides a comprehensive overview of current urine-based liquid biopsy platforms, with a focus on protein and RNA biomarkers in urological cancers. We highlight the clinical relevance of these biomarkers and discuss technological innovations-including multi-omics integration, machine learning applications, and point-of-care testing-that are expanding their diagnostic utility. By leveraging the unique anatomical accessibility of urological malignancies via urine sampling, this field is poised to significantly enhance precision oncology.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression profiling of flowering time pathway in the L-ascorbate peroxidase 9 (APX9) near-isogenic line derived from an interspecific cross between Korean Japonica rice (Oryza sativa L.) and Oryza rufipogon.","authors":"Yun-A Jeon, Hyun-Sook Lee, Cheryl Adeva, Sang-Nag Ahn, Kyu-Chan Shim","doi":"10.1007/s13258-025-01683-2","DOIUrl":"https://doi.org/10.1007/s13258-025-01683-2","url":null,"abstract":"<p><strong>Background: </strong>Flowering time (referred to as heading date in rice) is a characteristic controlled by quantitative trait loci (QTLs). Heading date is an important agronomic trait that determines yield in rice and is precisely regulated by various exogenous and endogenous factors.</p><p><strong>Objective: </strong>To investigate the role of the ascorbate peroxidase 9 (APX9) gene in the flowering mechanism, we examined the expression levels of flowering time regulators under long-day conditions (14 h light/10 hours dark) and natural long-day conditions.</p><p><strong>Methods: </strong>A BC₄F₇ near-isogenic line (NIL), derived from an interspecific cross between the Korean elite japonica cultivar (cv. Hwaseong, Oryza sativa L.) and Oryza rufipogon (IRGC 105491), was used in this study to identify and characterize candidate genes associated with heading traits. The NIL contains a small O. rufipogon chromosome segment harboring the APX9 gene. In addition, overexpression and T-DNA insertion knockout transgenic lines were used to examine the function of APX9 gene.</p><p><strong>Results: </strong>The NIL exhibited delayed flowering under both controlled and natural long-day conditions compared to Hwaseong. Real-time PCR analysis indicated that APX9 influences the upstream pathway of flowering time regulation. Over-expression lines showed delayed flowering relative to Hwaseong, whereas T-DNA mutants flowered earlier than the control cultivar, Dongjin. These findings support a role for APX9 in modulating flowering time in rice.</p><p><strong>Conclusion: </strong>The APX9 is known for its antioxidant activity and its response to various abiotic stresses. The APX9 may play a role in the upstream regulation of the flowering pathway. These findings will be valuable in understanding the effect of APX9 during flowering stages. It would also be interesting to explore the relationship between hydrogen peroxide (H₂O₂₎ levels and the APX9 gene in signaling events related to heading.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of microbiome markers for ordered groups.","authors":"Jaehong Yu, Md Mozaffar Hosain, Taesung Park","doi":"10.1007/s13258-025-01673-4","DOIUrl":"https://doi.org/10.1007/s13258-025-01673-4","url":null,"abstract":"<p><strong>Background: </strong>Identifying microbiome markers associated with ordered phenotypes, such as disease stages or severity levels, is crucial for understanding disease progression and advancing precision medicine. Despite this importance, most existing methods for differential abundance analysis are designed for binary group comparisons and do not incorporate ordinal information, limiting their ability to capture trends across ordered categories.</p><p><strong>Objective: </strong>To develop and evaluate statistical methods that explicitly account for ordinal phenotype structure in microbiome data, addressing challenges such as sparsity and zero inflation, and improving the detection of meaningful microbial associations.</p><p><strong>Methods: </strong>In this study, we propose and evaluate three novel approaches specifically tailored for microbiome association analysis with ordered groups: the binary optimal test, the linear trend test, and the proportional odds model-based permutation test (POMp). These methods explicitly account for the ordinal structure of phenotypes and address the sparsity and zero-inflation commonly observed in microbiome data through permutation-based inference. We applied the proposed methods to three publicly available gut microbiome datasets, including two related to obesity and one concerning colorectal cancer.</p><p><strong>Results: </strong>All three proposed methods successfully identified differentially abundant features (DAFs) that exhibited stronger ordinal associations compared to those identified by existing methods. In particular, POMp consistently outperformed other approaches in terms of correlation with phenotype order, demonstrating its potential to identify biologically relevant markers.</p><p><strong>Conclusion: </strong>The findings of this study highlight the importance of incorporating ordinal information in microbiome studies and provide robust statistical tools for advancing microbial biomarker discovery in complex disease contexts.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms of synovial pathology in osteoarthritis: insights from CXCL10 and MC4R expression.","authors":"Tao Yang, Hong Liu, Jian Chen","doi":"10.1007/s13258-025-01679-y","DOIUrl":"https://doi.org/10.1007/s13258-025-01679-y","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a common progressive joint disorder marked by synovial inflammation, cartilage degeneration, the formation of osteophytes, though its underlying molecular mechanisms remain unclear. This study integrated bioinformatics and experimental validation to identify key genes in OA synovium and their association with immune infiltration. Analysis of the GSE82107 dataset (10 OA, 7 controls) revealed 909 differentially expressed genes (525 upregulated, 384 downregulated). WGCNA identified the \"midnightblue\" module, and its intersection with DEGs yielded 122 genes enriched in cytokine-cytokine receptor interaction, JAK-STAT signaling, and autophagy pathways. Protein-protein interaction analysis highlighted FLT3LG, MC4R, CXCL10, CARTPT, and LHX2 as core genes (AUC 0.743-0.871). Immune infiltration analysis showed elevated M0 macrophages in OA, with CXCL10 showing a strong positive correlation with M1 macrophage infiltration (r = 0.74), and MC4R correlating with the presence of follicular helper T cells (r = 0.85). In vitro, OA-derived fibroblast-like synoviocytes exhibited CXCL10 upregulation, MC4R downregulation, and increased IL-6, IL-8, and TNF-α secretion, which were markedly reduced by CXCL10 knockdown or MC4R overexpression. Synovial tissue assays confirmed these expression patterns. CXCL10 and MC4R may represent promising diagnostic markers and therapeutic targets, offering new insights into OA immunopathogenesis and precision intervention.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The PAR-score based on PANoptosis genes predicts the progression of ulcerative colitis and the response to anti-TNF-α treatment.","authors":"Yantong Li, Xisheng Yin, Shi Zheng, Yong Zhao, Xiaolin Zhong","doi":"10.1007/s13258-025-01675-2","DOIUrl":"https://doi.org/10.1007/s13258-025-01675-2","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis (UC), a chronic inflammatory bowel disease, carries an elevated risk of colitis-associated colorectal cancer (CAC). While PANoptosis-a coordinated cell death mechanism integrating pyroptosis, apoptosis, and necroptosis-has been linked to inflammatory disorders, its role in UC progression and CAC transformation remains undefined.</p><p><strong>Objective: </strong>To delineate PANoptosis-related signatures and develop predictive models for the assessment of UC and CAC.</p><p><strong>Methods: </strong>Transcriptomic data from UC patients, CAC cases, and controls (GEO database) were analyzed to identify PANoptosis-associated genes. Enrichment and immune infiltration analyses elucidated functional roles, while a dextran sulfate sodium (DSS)-induced murine colitis model validated candidate gene expression via Western blot. Single-cell sequencing dissected cellular heterogeneity, Mendelian randomization established causality, and molecular docking screened therapeutic agents.</p><p><strong>Results: </strong>Four PANoptosis hub genes (CASP1, LCN2, STAT3, ZBP1) were identified as UC drivers. The PANoptosis-Associated Risk Score (PAR-Score) demonstrated robust diagnostic accuracy (AUC > 0.75) and stratified disease activity, anti-TNF-α responsiveness, and CAC risk. Molecular docking revealed strong binding affinity between epidermal growth factor receptor (EGFR) inhibitors and target proteins (binding energy: -6.0 to -8.4 kcal/mol), suggesting therapeutic potential.</p><p><strong>Conclusion: </strong>The PAR-Score based on PANoptosis genes predicts the progression of UC and the response to anti-TNF-α treatment. EGFR inhibitors may serve as potential therapeutic agents for UC and CAC.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of MSH2, MSH6, and MLH1 polymorphisms with susceptibility and survival in lung cancer patients.","authors":"Jing Cheng, Chao Zuo, Dongli Yang, Yi Liu, Yu Wang, Yongchao Qiao","doi":"10.1007/s13258-025-01681-4","DOIUrl":"https://doi.org/10.1007/s13258-025-01681-4","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer (LC) is the leading cause of cancer-related deaths globally. Genetic variants in mismatch repair (MMR) genes, such as MutS homolog 2 (MSH2), MutS homolog 6 (MSH6) and MutL homolog 1 (MLH1), may influence individual susceptibility and clinical outcomes in LC.</p><p><strong>Objective: </strong>This study investigated the associations of genetic polymorphisms in MSH2, MSH6, and MLH1 with susceptibility and survival outcomes in lung cancer patients in the Guangxi Zhuang population.</p><p><strong>Methods: </strong>This study included a cohort of 192 LC patients and 262 healthy controls. The association of MSH2, MSH6, and MLH1 polymorphisms with susceptibility to small cell lung cancer (SCLC), lung adenocarcinoma (LUAD), and lung squamous carcinoma (LUSC) was evaluated using case-control methods, and protein expression differences were analysed by immunohistochemistry. The genotypes of genetic variations were detected using high-throughput SNP-scan technology. The Kaplan-Meier survival curve and log-rank test were used to assess the influence of individual genetic variants on prognostic outcomes in lung cancer patients.</p><p><strong>Results: </strong>Multivariate logistic regression identified significant associations of rs2303428 and rs1042821 with increased lung cancer risk, especially in SCLC and LUSC. The GA and GG genotypes of rs1042821 were linked to higher SCLC risk (OR = 4.415 and 2.685; P = 0.019), the TC genotype of rs2303428 was associated with elevated LUSC risk (OR = 3.993; P = 0.034). No associations were found for rs1800734 or in LUAD. Immunohistochemistry showed increased MSH2 and MSH6 expression in risk genotypes, with no genotype-related changes in MLH1. In LUAD, the CC genotype of rs2300789 was associated with poorer overall survival compared to TC (P = 0.047), with no significant differences in other comparisons.</p><p><strong>Conclusion: </strong>rs2303428 and rs1042821 polymorphisms were associated with increased lung cancer susceptibility and altered protein expression. Additionally, the CC genotype of rs2300789 was linked to poorer overall survival in LUAD.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}