{"title":"Performance analysis of large language models Chatgpt-4o, OpenAI O1, and OpenAI O3 mini in clinical treatment of pneumonia: a comparative study.","authors":"Zhiwu Lin, Yuanyuan Li, Min Wu, Hongmei Liu, Xiaoyang Song, Qian Yu, Guibao Xiao, Jiajun Xie","doi":"10.1007/s10238-025-01743-7","DOIUrl":"10.1007/s10238-025-01743-7","url":null,"abstract":"<p><p>This study aimed to compare the performance of three large language models (ChatGPT-4o, OpenAI O1, and OpenAI O3 mini) in delivering accurate and guideline compliant recommendations for pneumonia management. By assessing both general and guideline-focused questions, the investigation sought to elucidate each model's strengths, limitations, and capacity to self-correct in response to expert feedback. Fifty pneumonia-related questions (30 general, 20 guideline-based) were posed to the three models. Ten infectious disease specialists independently scored responses for accuracy using a 5-point scale. The two chain-of-thought models (OpenAI O1 and OpenAI O3 mini) were further tested for self-correction when initially rated \"poor,\" with re-evaluations conducted one week later to reduce recall bias. Statistical analyses included nonparametric tests, ANOVA, and Fleiss' Kappa for inter-rater reliability. OpenAI O1 achieved the highest overall accuracy, followed by OpenAI O3 mini; ChatGPT-4o scored lowest. For \"poor\" responses, O1 and O3 mini both significantly improved after targeted prompts, reflecting the advantages of chain-of-thought reasoning. ChatGPT-4o demonstrated limited gains upon re-prompting and provided more concise, but sometimes incomplete, information. OpenAI O1 and O3 mini offered superior guideline-aligned recommendations and benefited from self-correction capabilities, while ChatGPT-4o's direct-answer approach led to moderate or poor outcomes for complex pneumonia queries. Incorporating chain-of-thought mechanisms appears critical for refining clinical guidance. These findings suggest that advanced large language models can support pneumonia management by providing accurate, up-to-date information, particularly when equipped to iteratively refine their outputs in response to expert feedback.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"213"},"PeriodicalIF":3.2,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332540","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":"Global and regional prevalence of osteoporosis in kidney transplant recipients: a systematic review and meta-analysis.","authors":"Mobin Ghazaiean, Tahoora Mousavi, Mahmood Moosazadeh","doi":"10.1007/s10238-025-01716-w","DOIUrl":"10.1007/s10238-025-01716-w","url":null,"abstract":"<p><p>Kidney transplant recipients (KTRs) are at a heightened risk of low bone density and fractures. This study sought to determine the overall prevalence of osteoporosis in KTRs. Published observational studies and those with a baseline report on osteoporosis were evaluated in databases such as PubMed, Scopus, Science Direct, Web of Science, and EMBASE, in addition to Google Scholar from January 1, 2000, to January 1, 2024. The methodological quality of the included studies was rigorously assessed using the JBI Critical Appraisal checklist. Heterogeneity across primary study results was evaluated using the I-square index, while publication bias was scrutinized using Egger's test and funnel plots. Statistical analyses were carried out using Stata software Ver. 11. After conducting searches across multiple databases, a total of 136 primary studies were ultimately included. The prevalence of osteoporosis in specific skeletal areas is as follows: 20% (95% CI 18-23, n = 67) in the lumbar region, 23% (95% CI 19-26, n = 53) in the femoral neck, 15% (95% CI 11-19, n = 20) in the total hip, 29% (95% CI 10-49, n = 5) in the forearm, and 34% (95% CI 28-40, n = 6) in the ultradistal radius. Based on sex-specific rate in the existing literature, the prevalence is reported as 21% (95% CI 15-27, n = 16) in men and 28% (95% CI 20-35, n = 16) in women. Our results for adult KTRs represent the high prevalence of osteoporosis which was highest in bone site rich in cortical content (e.g., ultradistal radius).</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"214"},"PeriodicalIF":3.2,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332539","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":"Evaluation and verification of MPDZ as a prognostic biomarker for hepatocellular carcinoma through multiple databases.","authors":"Jianzhu Luo, Jianhua Liang, Haixiang Xie, Jiaguang Chen, Xiaoqiang Shen, Fuquan Yang, Tianman Li","doi":"10.1007/s10238-025-01729-5","DOIUrl":"10.1007/s10238-025-01729-5","url":null,"abstract":"<p><p>The aim of this study was to assess the prognostic value of the multi-PDZ domain protein (MPDZ) in hepatocellular carcinoma (HCC). MPDZ expression in HCC and normal liver tissue samples were analyzed using TCGA-LIHC data and validated in the GSE14520, GSE62232, GSE76427, GSE121248, and GSE136247 datasets. MPDZ's prognostic value in HCC was evaluated based on Kaplan-Meier survival analysis and Cox proportional risk models. The correlation of MPDZ with other prognostic factors was explored by combined survival analysis and stratified survival analysis. The differentially expressed genes between patient groups stratified on the basis of MPDZ levels in TCGA-LIHC were screened using R and functionally annotated by the GO and KEGG pathway analysis by DAVID. Furthermore, gene set enrichment analysis was conducted to determine the basic molecular mechanism of MPDZ in HCC, and the protein-protein interactions, gene-gene interactions, and immune infiltration status of MPDZ was analyzed by STRING, GeneMania, and TIMER. Our findings indicate that MPDZ is downregulated in HCC and portends worse prognosis. Bioinformatics analysis revealed a strong link between MPDZ and liver cancer progression, liver cancer survival, multiple metabolic pathways, and multiple signaling pathways. In addition, our findings indicate that MPDZ expression is associated with several key genes in the ferroptosis pathway and m6A methylation. Finally, immunohistochemical assessment of clinical specimens confirmed low MPDZ protein expression in HCC tissues relative to paraneoplastic tissues. Taken together, MPDZ is a promising biomarker for the diagnosis and prognosis of HCC.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"209"},"PeriodicalIF":3.2,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324614","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}
Fengjie Qiao, Yan Xue, Chen Zou, Kun Liu, Jie Yuan, Longshan Ji, Lingying Huang, Man Li, Yueqiu Gao
{"title":"The application performance of MRI-PDFF detection values of different hepatic lobes in diagnosing liver steatosis.","authors":"Fengjie Qiao, Yan Xue, Chen Zou, Kun Liu, Jie Yuan, Longshan Ji, Lingying Huang, Man Li, Yueqiu Gao","doi":"10.1007/s10238-025-01739-3","DOIUrl":"10.1007/s10238-025-01739-3","url":null,"abstract":"<p><p>Magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) is becoming increasingly important for assessing liver steatosis, which is traditionally diagnosed via liver biopsy. In the present study, we aimed to evaluate the efficacy of MRI-PDFF in detecting liver steatosis by comparing its values from various liver lobes-the right posterior hepatic lobe (RPHL), right anterior hepatic lobe (RAHL), left inner hepatic lobe (LIHL), left outer hepatic lobe (LOHL), the mean value of four hepatic lobes (M-PDFF), and the highest value of four hepatic lobes (H-PDFF)-against biopsy results. The findings indicated that MRI-PDFF exhibited strong performances in identifying liver steatosis in 125 patients, with area under the receiver operating characteristic (AUROC) values of 0.870 for RPHL, 0.875 for RAHL, 0.881 for LIHL, 0.871 for LOHL, 0.881 for M-PDFF, and 0.878 for H-PDFF. Furthermore, MRI-PDFF demonstrated significant advantages in detecting moderate-to-severe steatosis, achieving AUROC values of 0.897 for RPHL, 0.911 for RAHL, 0.905 for LIHL, 0.898 for LOHL, 0.907 for M-PDFF, and 0.904 for H-PDFF. Overall, MRI-PDFF is a highly accurate and noninvasive tool for diagnosing liver steatosis and determining its severity, making it valuable for clinical assessment and treatment.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"210"},"PeriodicalIF":3.2,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324625","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}
Kiavash Hushmandi, Daniel J Klionsky, Najma Farahani, Russel J Reiter, Abbas Ali Imani Imani Fooladi, Mina Alimohammadi, Amir Reza Aref
{"title":"Regulation of pyroptosis in diabetic nephropathy by long non-coding and circular RNAs.","authors":"Kiavash Hushmandi, Daniel J Klionsky, Najma Farahani, Russel J Reiter, Abbas Ali Imani Imani Fooladi, Mina Alimohammadi, Amir Reza Aref","doi":"10.1007/s10238-025-01740-w","DOIUrl":"10.1007/s10238-025-01740-w","url":null,"abstract":"<p><p>Diabetic nephropathy (DN) is a major complication of diabetes mellitus, predominantly affecting the kidneys of diabetic patients and resulting in increased morbidity and mortality. Current standard treatments for diabetes have proven insufficient in halting the progression of DN, highlighting the urgent need for innovative and more effective therapeutic strategies. Pyroptosis, a pro-inflammatory regulated cell death process, has been previously associated with DN development. Recent evidence indicates that the NLRP3 inflammasome, a key inflammatory pathway complex, promotes DN through pyroptosis. Consequently, inhibiting inflammasome activity has emerged as a promising therapeutic target against DN, in conjunction with pyroptosis. This review introduces non-coding RNAs (ncRNAs), particularly circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs), as potential regulators of pyroptosis in DN, as recent studies have documented their dysregulation in DN pathogenesis. In this study, we aim to discuss the characteristics of lncRNAs, circRNAs, and pyroptosis and explore their potential interconnection in DN development. By elucidating the link between these RNA molecules and pyroptosis, our goal is to deepen our understanding of the underlying mechanisms of the disease. This knowledge could lead to the identification of new therapeutic targets and the development of innovative treatments for DN by modulating pyroptosis.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"208"},"PeriodicalIF":3.2,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324624","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":"Innovative technologies and their clinical prospects for early lung cancer screening.","authors":"Zisu Deng, Xiaocao Ma, Shubiao Zou, Liling Tan, Tingting Miao","doi":"10.1007/s10238-025-01752-6","DOIUrl":"10.1007/s10238-025-01752-6","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer remains the leading cause of cancer-related mortality worldwide, due to lacking effective early-stage screening approaches. Imaging, such as low-dose CT, poses radiation risk, and biopsies can induce some complications. Additionally, traditional serum tumor markers lack diagnostic specificity. This highlights the urgent need for precise and non-invasive early detection techniques.</p><p><strong>Purpose: </strong>This systematic review aims to evaluate the limitations of conventional screening methods (imaging/biopsy/tumor markers), seek breakthroughs in liquid biopsy for early lung cancer detection, and assess the potential value of Artificial Intelligence (AI), thereby providing evidence-based insights for establishing an optimal screening framework.</p><p><strong>Methods: </strong>We systematically searched the PubMed database for the literature published up to May 2025. Key words include \"Artificial Intelligence\", \"Early Lung cancer screening\", \"Imaging examination\", \"Innovative technologies\", \"Liquid biopsy\", and \"Puncture biopsy\". Our inclusion criteria focused on studies about traditional and innovative screening methods, with an emphasis on original research concerning diagnostic performance or high-quality reviews. This approach helps identify critical studies in early lung cancer screening.</p><p><strong>Conclusions: </strong>Novel liquid biopsy techniques are non-invasive and have superior diagnostic efficacy. AI-assisted diagnostics further enhance accuracy. We propose three development directions: establishing risk-based liquid biopsy screening protocols, developing a stepwise \"imaging-AI-liquid biopsy\" diagnostic workflow, and creating standardized biomarker panel testing solutions. Integrating traditional methodologies, novel liquid biopsies, and AI to establish a comprehensive early lung cancer screening model is important. These innovative strategies aim to significantly increase early detection rates, substantially enhancing lung cancer control. This review provides both theoretical guidance for clinical practice and future research.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"212"},"PeriodicalIF":3.2,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324623","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}
Alaa M Mostafa, Yasser Fouad, Yasmine Gaber, Shereen Abdel Alem, Ziyan Pan, Mohammed Eslam
{"title":"Differential risk factors of fibrosis between lean and obese MAFLD.","authors":"Alaa M Mostafa, Yasser Fouad, Yasmine Gaber, Shereen Abdel Alem, Ziyan Pan, Mohammed Eslam","doi":"10.1007/s10238-025-01749-1","DOIUrl":"10.1007/s10238-025-01749-1","url":null,"abstract":"<p><p>Metabolic dysfunction-associated fatty liver disease (MAFLD) is often linked to overweight and obesity. However, a significant number of individuals with MAFLD are not obese, commonly referred to as lean MAFLD. This study aims to investigate the potential risk factors for fibrosis among lean individuals with MAFLD compared to those who are overweight or obese. The study included 7902 participants from the National Health and Nutrition Examination Survey (NHANES) data collected between 2017 and March 2020. MAFLD was defined in individuals with steatosis who were either overweight, diabetic, or lean and had at least two metabolic risk abnormalities. Demographic, anthropometric, and laboratory data, along with elastography results, were reported for each subject. Lean patients with MAFLD were significantly older (62.3 ± 13.8 years) compared to overweight or obese patients with MAFLD (51.7 ± 16.7 years; p < 0.001). Several factors were identified as predictors of significant fibrosis within the MAFLD population, including increasing age, BMI, ALT levels, alkaline phosphatase levels, lower platelet counts, lower HDL-cholesterol levels, and the presence of diabetes. In a multivariate logistic analysis of significant fibrosis (F > 2) in patients with obese MAFLD, female gender, diabetes, and hypertension were identified as risk factors. For lean individuals with MAFLD, older age, high AST levels, and lower platelet counts were found to be significant predictors of fibrosis. MAFLD among lean individuals is not a benign condition; those with metabolic dysfunction are at risk of developing fibrosis. The risk factors for fibrosis in these individuals may differ from those in their obese counterparts.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"211"},"PeriodicalIF":3.2,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12177025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324613","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":"Clinicopathological features and renal outcomes in patients with IgA nephropathy secondary to psoriasis.","authors":"Dafeng He, Guangyu Bi, Hongbin Mou, Rong Wang, Chunlei Lu, Zheng Tang","doi":"10.1007/s10238-025-01750-8","DOIUrl":"10.1007/s10238-025-01750-8","url":null,"abstract":"<p><p>Few studies have examined the features of patients with IgA nephropathy secondary to psoriasis (IgAN-Pso); leaving the long-term renal outcomes and risk factors for this group unclear. A total of ninety patients with IgAN without evidence of a secondary cause other than psoriasis were enrolled in this retrospective study. The participants were categorized into two groups: the mild-to-moderate psoriasis group (n = 74) and the severe psoriasis group (n = 16). A comparative analysis was conducted on the clinicopathological attributes and renal outcomes between the two groups. Additionally, prognostic risk factors for end-stage renal disease (ESRD) were assessed. The patients within the severe psoriasis cohort exhibited a heightened prevalence of eGFR < 60 ml/min/1.73 m<sup>2</sup> and urinary protein levels exceeding 1.49 g/d, alongside more pronounced T lesions and an increased incidence of C2 lesions (crescent > 25%) compared to their mild-to-moderate psoriasis counterparts. During a median follow-up period of 34.8 months, 11 patients (5 [35.7%] with severe psoriasis and 6 [8.2%] with mild-moderate psoriasis, P < 0.05) progressed to ESRD. At the time of biopsy, eGFR, CRP > 21.2 mg/l, immunoglobulin G > 8.05 g/l, low C3 and time-average proteinuria emerged as independent predictors of future ESRD. Pathological parameters could not independently predict ESRD when considering the baseline clinical features. Our study indicates that severe psoriasis is associated with worse renal impairment observed at biopsy and a greater likelihood of developing ESRD afterwards.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"207"},"PeriodicalIF":3.2,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316027","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":"β-catenin as a key regulator of the cisplatin response in tumor cells.","authors":"Ehsan Saburi, Meysam Moghbeli","doi":"10.1007/s10238-025-01757-1","DOIUrl":"10.1007/s10238-025-01757-1","url":null,"abstract":"<p><p>Chemotherapy is one of the most frequent therapeutic options in cancer patients. Cisplatin (CDDP) is widely used as one of the first-line platinum-based drugs in metastatic tumors. However, CDDP resistance is always one of the main therapeutic challenges in cancer patients. Considering the side effects of CDDP in cancer patients, the prediction of CDDP response can improve the management of tumor therapy. Therefore, it is necessary to investigate the molecular mechanisms involved in CDDP resistance in order to predict CDDP response in cancer patients. CDDP resistance is contributed with different cellular processes such as DNA repair, drug efflux, and signaling pathways. WNT/β-catenin pathway has a key role in tumor growth and drug resistance. β-catenin is considered as a key component of the WNT pathway, which can regulate the CDDP response in tumor cells by regulation of WNT target genes. In addition to the WNT pathway, β-catenin can also be regulated by the other signaling pathways. Deregulation of β-catenin is associated with CDDP resistance. Therefore, in the present review, we discussed the role of β-catenin in regulation CDDP response in tumor cells. It has been reported that β-catenin mainly promotes CDDP resistance in various cancers, whose function can be affected by other signaling pathways and transcription factors. This review can be an effective step toward introducing β-catenin as a prognostic marker as well as a therapeutic target in CDDP-resistant cancer patients.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"206"},"PeriodicalIF":3.2,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12167723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301233","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":"HNF4A promotes tumor progression in gastric cancer by transcriptional activation of KIF2C.","authors":"Hao Lu, Jin-Heng Gan, Li-Qiang Zhou, Yi-Wu Yuan, Qi Zhou, Lin Xin","doi":"10.1007/s10238-025-01748-2","DOIUrl":"10.1007/s10238-025-01748-2","url":null,"abstract":"<p><p>Hepatocyte nuclear factor 4A (HNF4A) is a core transcription factor that plays an important role in tumor progression. However, the regulatory mechanisms in gastric cancer remain unclear. In this study, we employed a bioinformatics-driven approach and combined it with cellular and animal experiments to investigate the regulatory mechanisms of HNF4A in gastric cancer. We identified kinesin family member 2C (KIF2C) as a novel downstream target of HNF4A and observed that both HNF4A and KIF2C were significantly upregulated in gastric cancer tissues. Knockdown of HNF4A or KIF2C inhibited the proliferation, migration, and invasion abilities of gastric cancer cells, while overexpression of KIF2C rescued these abilities of sh-HNF4A in gastric cancer cells. Mechanistically, HNF4A and KIF2C were found to colocalize in the nucleus, with HNF4A directly binding to the KIF2C promoter. Further analysis identified BS2 (-1381 ~ -1368) and BS3 (-715 ~ -700) as the core binding regions. In vivo experiments demonstrated that knockdown HNF4A inhibited tumor growth in BALB/c nude mice, and overexpression of KIF2C promoted tumor growth. In conclusion, HNF4A is an oncogene that promotes the proliferation, migration, and invasion of gastric cancer cells. Our study suggests that HNF4A can transcriptionally activate KIF2C and that the HNF4A-KIF2C axis may be a potential therapeutic target for gastric cancer.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"205"},"PeriodicalIF":3.2,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12167340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293449","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}