Clinical and Experimental Medicine最新文献

{"title":"Macrophages in graft-versus-host disease (GVHD): dual roles as therapeutic tools and targets.","authors":"Atieh Raoufi, Hamed Soleimani Samarkhazan, Sina Nouri, Mohammad Navid Khaksari, Parvaneh Abbasi Sourki, Omolbanin Sargazi Aval, Behzad Baradaran, Mojtaba Aghaei","doi":"10.1007/s10238-025-01588-0","DOIUrl":"10.1007/s10238-025-01588-0","url":null,"abstract":"<p><p>Graft-versus-host disease remains one of the most formidable barriers to the complete success of hematopoietic stem cell transplantation that has emerged as the curative approach for many hematopoietic malignancies because it affects quality of life and overall survival. Macrophages are among the important members of the immune system, which perform dual roles in GVHD as both therapeutic tools and targets. This review epitomizes the multifunctional role of macrophages in the pathophysiology of both acute and chronic GVHD. Macrophages play an important role in the early phase of GVHD because of their recruitment and infiltration into target organs. Furthermore, they polarize into two functionally different phenotypes, including M1 and M2. In the case of acute GVHD, most macrophages express the M1 phenotype characterized by the production of pro-inflammatory cytokines that contribute to tissue damage. In contrast, in chronic GVHD, macrophages tend toward the M2 phenotype associated with the repair of tissues and fibrosis. A critical balance among these phenotypes is central to the course and severity of GVHD. Further interactions of macrophages with other lymphocytes such as T cells, B cells, and fibroblast further determine the course of GVHD. Macrophage interaction associated with alloreactive T cells promotes inflammation. This is therefore important in inducing injuries of tissues during acute GVHD. Interaction of macrophages, B cell, fibroblast, and CD4+ T cells promotes fibrosis during chronic GVHD and, hence, the subsequent dysfunction of organs. These are some insights, while several challenges remain. First, the impact of the dominant cytokines in GVHD on the polarization of macrophages is incompletely characterized and sometimes controversial. Second, the development of targeted therapies able to modulate macrophage function without systemic side effects remains an area of ongoing investigation. Future directions involve the exploration of macrophage-targeted therapies, including small molecules, antibodies, and nanotechnology, which modulate macrophage behavior and improve patient outcomes. This underlines the fact that a profound understanding of the dual role of macrophages in GVHD is essential for developing new and more effective therapeutic strategies. Targeting macrophages might represent one avenue for decreasing the incidence and severity of GVHD and improving the success and safety of HSCT.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"73"},"PeriodicalIF":3.2,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566219","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":"Advances in risk prediction models for cancer-related cognitive impairment.","authors":"Ran Duan, ZiLi Wen, Ting Zhang, Juan Liu, Tong Feng, Tao Ren","doi":"10.1007/s10238-025-01590-6","DOIUrl":"10.1007/s10238-025-01590-6","url":null,"abstract":"<p><p>Cancer-related cognitive impairment (CRCI) has emerged as a significant long-term complication in cancer survivors, particularly those undergoing chemotherapy, radiotherapy, or targeted therapies. Despite advances in treatment, CRCI affects patients' quality of life, impacting their daily functioning, work capacity, and psychological well-being. In recent years, research has focused on identifying predictive factors for CRCI and developing risk prediction models to facilitate early intervention. This review summarizes the latest progress in CRCI risk prediction models, including traditional statistical approaches such as logistic regression and advanced machine learning techniques. While machine learning models demonstrate superior predictive performance, limitations such as data availability and model interpretability remain. Additionally, the review highlights key risk factors-such as age, cancer type, and treatment modalities-and evaluates the strengths and weaknesses of various predictive models in terms of accuracy, generalizability, and clinical applicability. Finally, this paper discusses the challenges in validating these models across diverse populations and the need for further research to enhance model reliability and personalization of interventions.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"74"},"PeriodicalIF":3.2,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566206","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 relationship between telomere length and aging-related diseases.","authors":"Xuanqi Huang, Leyi Huang, Jiaweng Lu, Lijuan Cheng, Du Wu, Linmeng Li, Shuting Zhang, Xinyue Lai, Lu Xu","doi":"10.1007/s10238-025-01608-z","DOIUrl":"10.1007/s10238-025-01608-z","url":null,"abstract":"<p><p>The intensifying global phenomenon of an aging population has spurred a heightened emphasis on studies on aging and disorders associated with aging. Cellular senescence and aging are known to be caused by telomere shortening. Telomere length (TL) has emerged as a biomarker under intense scrutiny, and its widespread use in investigations of diseases tied to advancing age. This review summarizes the current knowledge of the association between telomeres and aging-related diseases, explores the important contribution of dysfunctional telomeres to the development and progression of these diseases, and aims to provide valuable insights for the development of novel therapeutic strategies.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"72"},"PeriodicalIF":3.2,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566220","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":"Efficacy and safety analysis of atezolizumab continuation beyond progression in extensive-stage small cell lung cancer.","authors":"Wenhao Shi, Xiaohui Bao, Jin Xiong, Yanqiao Wu, Jianguo Sun, Zhi Xu, Dairong Li, Yang Wei, Jun Ge, Biyong Ren, Yu Jiang, Kaijin Wang, Yusheng Huang, Zhenzhou Yang, Yuan Peng","doi":"10.1007/s10238-025-01606-1","DOIUrl":"10.1007/s10238-025-01606-1","url":null,"abstract":"<p><p>The advent of immune checkpoint inhibitors (ICIs) has revolutionized the treatment landscape for extensive-stage small cell lung cancer (ES-SCLC) patients. However, many patients eventually develop resistance to immunotherapy. While continued ICI therapy beyond disease progression has shown survival benefits in various cancers, research specific to ES-SCLC remains limited. Our study aimed to further evaluate the efficacy and safety of atezolizumab continuation therapy to optimize the ICI continuation strategies for ES-SCLC. In this multicenter study, all enrolled patients received continued atezolizumab in combination therapy as second-line (2L) treatment after progression of first-line (1L) chemo-immunotherapy. The efficacy was measured by median overall survival (mOS) and median progression-free survival (mPFS). Safety was evaluated based on incidence of adverse events (AEs). Among the 28 eligible patients in this study, mPFS was 4.07 months [95% CI: 1.15 to 6.98], and mOS was 18.87 months [95% CI: 15.28 to 22.45]. In the safety analysis, respiratory-related AEs were the most common, including cough (35.7%), dyspnea (35.7%), pneumonitis (35.7%). Additionally, thyroiditis (17.9%) was the most generally reported immune-related adverse events (irAEs). In subgroup analysis, the LTR group (1L-PFS ≥ 6 months) showed longer mOS compared with the STR group (1L-PFS < 6 months) [19.98 vs. 8.68 months, p = 0.021]. Patients with greater DpR (≥ 29% than < 29%) had longer mOS: 21.84 vs. 14.63, p < 0.01]. Atezolizumab continuation therapy demonstrated promising efficacy and manageable safety in ES-SCLC patients progressing after 1L chemo-immunotherapy, particularly in those with favorable 1L treatment responses.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"71"},"PeriodicalIF":3.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556082","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 value of plasma sCD25 in diagnosis, therapeutic efficacy, and prognosis of acute myeloid leukemia.","authors":"JiaYi Wang, YuanLing Zuo, Wen Wang, Jie Xu, Cuiping Liu, Min Jiang","doi":"10.1007/s10238-025-01557-7","DOIUrl":"10.1007/s10238-025-01557-7","url":null,"abstract":"<p><p>This study aims to investigate the clinical importance of soluble CD25 (sCD25) levels in diagnosing acute myeloid leukemia (AML), predicting patient outcomes, and monitoring treatment responses. Plasma sCD25 levels were measured in 190 AML patients and 47 healthy controls. AML patients were further divided into subgroups based on chemotherapy status, therapeutic response, and prognostic risk. Statistical analyses were performed to investigate the relationships between sCD25 levels and various clinical parameters, along with its potential diagnostic and prognostic significance. Plasma sCD25 levels were significantly elevated in AML patients compared to healthy controls (p < 0.0001). High sCD25 levels correlated positively with white blood cell count, age, and pulmonary infection (p < 0.01) and negatively with hemoglobin and platelet counts (p < 0.01). Logistic regression analysis identified sCD25 as a risk factor for both AML diagnosis (OR = 59.240, 95% CI: 11.14-315.0, p < 0.0001) and poor prognosis (OR = 1.651, 95% CI: 1.094-2.492, p < 0.05). ROC curve analysis demonstrated that sCD25 has high diagnostic accuracy for AML (AUC = 0.929, sensitivity = 86.44%, specificity = 93.62%) and moderate predictive value for chemotherapy non-remission (AUC = 0.66, p < 0.05). Plasma sCD25 levels are significantly elevated in AML and show potential as a diagnostic and prognostic biomarker. sCD25 may also be useful for monitoring treatment response in AML patients. Further studies are warranted to elucidate its role in AML pathogenesis.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"70"},"PeriodicalIF":3.2,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539433","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":"Prediction of vedolizumab efficacy in ulcerative colitis: a nomogram incorporating pathological feature and serological marker.","authors":"Tian Wang, Min Zou, Chaoqun Hu, Yan Liu, Wei Tan, Xiaomei Song, Yongsheng Teng, Hui Yao, Xuefeng Tang, Hong Guo","doi":"10.1007/s10238-025-01601-6","DOIUrl":"10.1007/s10238-025-01601-6","url":null,"abstract":"<p><p>Vedolizumab (VDZ) is a humanized, gut-selective biologic used in the treatment of ulcerative colitis (UC). However, data on predictive factors for treatment response are limited. This study aims to develop a nomogram to predict VDZ treatment responsiveness in UC. We retrospectively collected clinical data from patients with moderate-to-severe active UC who received VDZ induction therapy at Chongqing General Hospital from December 2020 to March 2024. Full-slide images of colon biopsies from UC patients prior to VDZ treatment were analyzed to quantify mean mucosal eosinophil density (MMED). Based on clinical response 14-week post-treatment, patients were categorized into responsive and non-responsive groups. In total, 84 UC patients were analyzed, with 58 responding to VDZ treatment and 26 not responding. Significant differences were observed in pathological indices, with MMED showing a statistically significant difference between the groups (p < 0.001). Serum biomarkers, including C-reactive protein (CRP), also showed a significant difference (P = 0.015), as did the CRP/albumin (CRP/ALB) ratio (P = 0.018). Additionally, UCEIS scores differed significantly between the groups (P = 0.025). Independent risk factors identified through multivariate logistic regression analysis were used to establish a predictive model, presented as a nomogram. The area under the curve (AUC) for the combined MMED and CRP predictive model was 0.867 (95% CI: 0.781-0.953, p < 0.001), indicating high accuracy in predicting VDZ efficacy. These data are easily accessible even in primary healthcare settings, allowing our predictive model to support improved treatment decisions for patients.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"69"},"PeriodicalIF":3.2,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536690","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":"Amiodarone-induced ocular and extra-ocular toxicity: a retrospective cohort study.","authors":"Rosanna Dammacco, Silvana Guerriero, Giuseppina Cardia, Giovanni Alessio, Angelo Vacca, Franco Dammacco","doi":"10.1007/s10238-025-01569-3","DOIUrl":"10.1007/s10238-025-01569-3","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Amiodarone (AMD) is a largely employed anti-arrhythmic agent for the treatment of recurrent supraventricular and ventricular tachyarrhythmias. Because of its lipophilic properties, prolonged half-life and prevailing biliary excretion, it is not rarely responsible for potentially severe adverse events that can involve one or more organs with a prevalence ranging from 15% in the first year of drug intake to 50% in patients treated for a longer time. In addition to pro-arrhythmia effects, AMD toxicity may result in a variable combination of clinical manifestations, including visual impairment, thyroid dysfunctions, pulmonary diseases, liver injury, neutropenia or thrombocytopenia. We aimed to describe the AMD-induced ophthalmologic and non-ophthalmologic side effects observed in a longitudinal cohort of patients. Seventeen Caucasian patients, who were on amiodarone therapy for a variable period, were enrolled in this retrospective, cross-sectional, observational study. All of them were referred to the Department of Ophthalmology and Neuroscience of the University of Bari, Italy, because of visual disturbances of variable severity. Three patients were given 3 intravenous boluses of 150 mg AMD followed by progressively decreasing oral doses, whereas 14 patients received a loading daily dose of 600-1200 mg orally, reduced after 2-3 weeks to a maintenance daily dose of 200-400 mg. All patients underwent complete clinical and laboratory assessments, according to a standard protocol. Ophthalmologic examination included intraocular pressure, ocular motility, visual field testing, angiography, optical coherence tomography, best-corrected visual acuity (BCVA) and grading of AMD-induced keratopathy by slit-lamp biomicroscopy. At diagnosis, eye disorders ranging from blurred vision and deterioration of visual acuity to eye redness and progressive glare were reported in 14 patients and lasting photophobia in the remaining 3 patients. Verticillate keratopathy (VK), stage 1-4, was diagnosed in all of them. Following AMD cessation, the patients were checked after a mean of 94 days and clear corneas were found in 12 of them, whereas lower-stage VK persisted in 5 patients. A 20/40 visual outcome or better was detected in 29 of 34 eyes (85.3%). Bilateral optic disk edema was found in 3 patients. Fundoscopic examination performed 23 months after AMD discontinuation showed that optic disk edema was reduced in all 3 patients, though to a variable extent. Optic neuropathy with protracted disk edema was diagnosed in a single patient who complained of progressive visual loss. Almost 2 months after AMD cessation, disk edema was reduced in OD &gt; OS and BCVA partially improved. Extra-ocular manifestations included poorly symptomatic hypothyroidism in 2 patients, and overt myxedema, cholestatic liver injury, pancytopenia and interstitial pneumonitis associated with subclinical hypothyroidism in one patient each. A point stemming from our study and not clearly emphasized i","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"68"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536686","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":"Critical roles of miR-21 in promotions angiogenesis: friend or foe?","authors":"Mohamed J Saadh, Nisreen Yasir Jasim, Mareb Hamed Ahmed, Suhas Ballal, Abhishek Kumar, Shikha Atteri, Raghav Vashishth, Jasur Rizaev, Ahmed Alhili, Mahmood Jasem Jawad, Farzaneh Yazdi, Amirali Salajegheh, Reza Akhavan-Sigari","doi":"10.1007/s10238-025-01600-7","DOIUrl":"10.1007/s10238-025-01600-7","url":null,"abstract":"<p><p>MiRNAs are small RNA strands that are managed following transcription and are of substantial importance in blood vessel formation. It is essential to oversee the growth, differentiation, death, movement and construction of tubes by angiogenesis-affiliated cells. If miRNAs are not correctly regulated in regard to angiogenesis, it can deteriorate the health and lead to various illnesses, which include cancer, cardiovascular disorder, critical limb ischemia, Crohn's disease, ocular diseases, diabetic microvascular complications, and more. Consequently, it is vital to understand the crucial part that miRNAs play in the development of blood vessels, so we can develop reliable treatment plans for vascular diseases. This write-up will assess the critical role of miR-21/exosomal miR-21 in managing angiogenesis associated with bone growth, wound recovery, and other pathological conditions like tumor growth, ocular illnesses, diabetes, and other diseases connected to formation of blood vessels. Previous investigations have demonstrated that miR-21 is present at higher amounts in certain cancerous cells, and it influences a multitude of genes that moderate the increased creation of blood vessels. Furthermore, studies demonstrated that exosomal miR-21 has the capacity to interact with endothelial cells to foster tumor angiogenesis. For that reason, this review explains the critical importance of miR-21/exosomal miR-21 in managing both healthy and diseased states of angiogenesis.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"66"},"PeriodicalIF":3.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491133","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":"Activation of RHO-GTPase gene pattern correlates with adverse clinical outcome and immune microenvironment in clear cell renal cell carcinoma.","authors":"Kehang Guo, Pengyue Ma, Qi Yang, Lingli Xu, Biixiong Zhang, Hong Zhang, Zhongwen Zheng, Zewei Zhuo","doi":"10.1007/s10238-025-01593-3","DOIUrl":"10.1007/s10238-025-01593-3","url":null,"abstract":"<p><p>Clear cell renal cell carcinoma (ccRCC), the most prevalent renal cancer subtype, is frequently associated with poor prognosis. RHO-GTPase signaling genes have been implicated in tumor aggressiveness and unfavorable survival, but their potential in risk stratification and therapeutic guidance for ccRCC patients remains unexplored. Univariate regression identified prognostically relevant RHO-GTPase signaling genes, followed by consensus clustering for ccRCC subtype classification. LASSO regression selected key genes to construct a six-gene risk model. The model was evaluated for prognostic stratification, immune status, immunotherapy response, and chemotherapy sensitivity. Key genes were analyzed at the genomic, single-cell, and protein levels to explore underlying mechanisms. Among 62 prognostically relevant RHO-GTPase signaling genes, six (ARHGAP11B, NUF2, PLK1, CYFIP2, IQGAP2, and VAV3) were identified to form a robust prognostic signature. This model stratified patients into high- and low-risk groups, with high-risk patients demonstrating significantly worse outcomes. The model exhibited excellent predictive accuracy (AUC > 0.7 in training and validation cohorts). High-risk patients were characterized by an immunosuppressive microenvironment and reduced sensitivity to immunotherapy. Drug sensitivity analysis revealed 107 agents correlated with the risk score, underscoring therapeutic relevance. Mechanistically, the six key genes showed distinct expression patterns, cellular distribution, and positive correlation with VHL mutations, highlighting their potential as actionable drug targets. This study established a novel six-gene RHO-GTPase signaling model for predicting prognosis, immune status, and therapeutic responses in ccRCC, which offers potential for improving patient stratification and guiding personalized treatment strategies.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"67"},"PeriodicalIF":3.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491127","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":"YY1-mediated DUXAP8 facilitates HCC progression via modulating DEPDC1 expression.","authors":"Yi Cui, Yong Sun, Na Liang, Chuan Tian","doi":"10.1007/s10238-025-01572-8","DOIUrl":"10.1007/s10238-025-01572-8","url":null,"abstract":"<p><p>The long noncoding RNA DUXAP8 has been implicated in the progression of various malignancies, including hepatocellular carcinoma (HCC). Although there is increasing evidence of DUXAP8's role in tumor biology, the exact mechanisms by which it affects the development and treatment of HCC are still unclear. Previous studies have suggested a potential link between DUXAP8 expression and disease progression, necessitating further investigation into its roles and underlying mechanisms. To clarify how DUXAP8 is involved in HCC, we measured its expression in HCC cell lines and tissues from patients. We utilized in vitro assays to evaluate the effects of DUXAP8 on tumor cell proliferation and metastasis. Additionally, we examined the regulatory relationships between DUXAP8, YY1, and DEPDC1 using RNA immunoprecipitation and luciferase reporter assays to investigate their functional mechanisms. Our findings demonstrated that DUXAP8 is frequently upregulated in HCC specimens and that its overexpression significantly enhances both the proliferation and metastatic capability of HCC cells. Importantly, the expression levels of DUXAP8, YY1, and DEPDC1 showed correlations with clinical parameters such as disease stage and histopathological characteristics. Mechanistically, we uncovered that YY1 regulates DUXAP8, which, in turn, modulates DEPDC1 expression through a dual mechanism involving the sponging of miR-7-5p and the stabilization of DEPDC1 mRNA facilitated by HNRNPF. Our study identifies DUXAP8 as a pivotal factor in the proliferation and metastasis of HCC, acting through the DUXAP8/miR-7-5p and DUXAP8/HNRNPF pathways to regulate DEPDC1 expression. These findings indicate that targeting DUXAP8 could be a new therapeutic strategy for treating HCC. Further research in both preclinical and clinical settings is needed to evaluate its potential as a biomarker and therapeutic target in liver cancer management.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"65"},"PeriodicalIF":3.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482264","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}