Journal of Translational Medicine最新文献

{"title":"Gene expression analysis in circulating tumour cells to determine resistance to CDK4/6 inhibitors plus endocrine therapy in HR + /HER2- metastatic breast cancer patients.","authors":"Miriam González-Conde, Celso Yáñez, Carmen Abuín, Corinna Keup, Ramón Lago-Lestón, Maribel Aybar, Lucía Pedrouzo, Patricia Palacios, Teresa Curiel, Juan Cueva, Carmela Rodríguez, Marta Carmona, Alexandra Cortegoso, Tomás García-Caballero, Laura Muinelo-Romay, Sabine Kasimir-Bauer, Rafael López-López, Clotilde Costa","doi":"10.1186/s12967-025-06374-w","DOIUrl":"10.1186/s12967-025-06374-w","url":null,"abstract":"<p><strong>Background: </strong>Metastatic breast cancer (BC) is the main cause of cancer-related mortality in women worldwide. HR + /HER2- BC patients are treated with endocrine therapy (ET), but therapeutic resistance is common. The combination of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with ET was approved for metastatic BC patients and extended the median progression-free survival to 24 months. This therapy is not always effective, and in every patient, resistance ultimately occurs, but the underlying resistance mechanisms remain unclear. To address this gap, we explored circulating tumour cells (CTCs) as biomarkers to assess treatment response and resistance in metastatic HR + /HER2- BC patients receiving CDK4/6i plus ET.</p><p><strong>Methods: </strong>In total, 53 HR + /HER2- metastatic BC patients who received a CDK4/6i plus ET as first-line treatment were analysed, including samples from internal and external validation cohorts. CTCs were isolated using the negative enrichment approach RosetteSep (STEMCELL Technologies) or positive immunomagnetic selection targeting EpCAM, EGFR, and HER2 (AdnaTest EMT-2/StemCell Select™, QIAGEN). RNA was extracted from CTCs and PBMCs for nCounter analysis (Pancancer pathways panel) in a discovery phase. Subsequent validation was performed by RT-qPCR.</p><p><strong>Results: </strong>CTC gene expression analysis revealed that non responder patients (those who experienced disease progression before 180 days) exhibited elevated PRKCB (p-value: 0.011), MAPK3 (p-value: 0.006) and STAT3 (p-value: 0.008) expression, while responders showed increased CDK6 (p-value: 0.011) and CCND1 (p-value: 0.035) expression at baseline. CTC transcriptional characterization revealed a gene expression signature (STAT3^highPRKCB^highCDK6^low) that accurately classified HR + /HER2- metastatic BC patients who responded to CDK4/6i plus ET, regardless of the CTC isolation method (AUC > 0.8). CTC characterization at progression also identified biomarkers linked to therapy resistance, including the epigenetic regulators EZH2 and HDAC6 and the cell cycle regulator CDC7, which could guide the selection of subsequent therapy lines. The expression of the CDK4 and STAT3 genes in CTCs was associated with progression-free survival and overall survival, respectively. Likewise, the presence of ≥ one CTC after one cycle of therapy predicts a worse prognosis.</p><p><strong>Conclusions: </strong>CTC gene expression provides information about treatment outcomes in HR + /HER2- metastatic BC patients receiving CDK4/6i plus ET and could guide personalized strategies and improve prognosis.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"400"},"PeriodicalIF":6.1,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 comparison of CAR-T and blinatumomab immunotherapy as bridge-to-transplant strategies in relapsed/refractory B cell acute lymphoblastic leukemia.","authors":"Wenyue Cao, Ningwen Li, Gaoxiang Wang, Hao Xu, Yang Yang, Jue Wang, Jinhuan Xu, Yun Li, Yicheng Zhang, Yang Cao, Na Wang","doi":"10.1186/s12967-025-06399-1","DOIUrl":"10.1186/s12967-025-06399-1","url":null,"abstract":"<p><strong>Background: </strong>Despite recent advances, B cell acute lymphoblastic leukemia (B-ALL) remains a therapeutic challenge. Hematopoietic stem cell transplantation (HSCT) provides a potential cure but is hindered by various limitations. Emerging immunotherapies, including chimeric antigen receptor T cell (CAR-T) therapy and blinatumomab, have shown potential as bridging strategies to HSCT in relapsed/refractory (R/R) patients.</p><p><strong>Methods: </strong>This retrospective study was conducted at Tongji Hospital from March 2017 to March 2023 and involved 36 R/R B-ALL patients who underwent HSCT. Prior to transplantation, 27 patients received CD19/CD22 CAR-T therapy, while 9 received blinatumomab. The outcomes assessed included overall survival (OS), progression-free survival (PFS), graft-versus-host disease-free and relapse-free survival (GRFS), and non-relapse mortality (NRM), with comparisons between treatment groups. Hematopoietic reconstitution and transplant-related complications were also evaluated.</p><p><strong>Results: </strong>The median follow-up time was 28.07 months (range: 2.29-92.21 months). The 2-year OS, PFS, GRFS, and NRM rates of the entire cohort were 76.54%, 54.97%, 40.12%, and 9.93%, respectively. In the CAR-T and blinatumomab treatment groups before transplantation, the 2-year OS rates were 73.89% and 88.89% (P = 0.862), the PFS rates were 59.03% and 44.44% (P = 0.501), the GRFS rates were 47.86% and 13.89% (P = 0.083), and the NRM rates were 8.52% and 11.11% (P = 0.713), respectively. The safety profiles were similar, with no significant differences observed in hematopoietic reconstitution, infection, incidence of grade II-IV acute graft-versus-host disease (GVHD), or chronic GVHD incidence between the CAR-T and blinatumomab groups.</p><p><strong>Conclusion: </strong>CAR-T and blinatumomab therapies demonstrate comparable safety and efficacy as bridging treatments to HSCT in patients with R/R B-ALL. Further studies are needed to optimize these treatment strategies.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"391"},"PeriodicalIF":6.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of human brain RNA-seq data reveals combined effects of 4 types of RNA modifications and 18 types of programmed cell death on Alzheimer's disease.","authors":"Ke Ye, Xinyu Han, Mengjie Tian, Lulu Liu, Xu Gao, Qing Xia, Dayong Wang","doi":"10.1186/s12967-025-06324-6","DOIUrl":"10.1186/s12967-025-06324-6","url":null,"abstract":"<p><strong>Background: </strong>RNA modification plays a critical role in Alzheimer's disease (AD) by modulating the expression and function of AD-related genes, thereby affecting AD occurrence and progression. Programmed cell death is closely related to neuronal death and associated with neuronal loss and cognitive function changes in AD. However, the mechanism of their joint action on AD remains unknown and requires further exploration.</p><p><strong>Methods: </strong>We used the MSBB RNA-seq dataset to analyze the correlation between RNA modification, programmed cell death, and AD. We used combined studies of RNA modification and programmed cell death to distinguish subgroups of patients, and the results highlight the strong correlation between RNA modification-related programmed cell death and AD. A weighted gene co-expression network was constructed, and the pivotal roles of programmed cell death genes in key modules were identified. Finally, by combining unsupervised consensus clustering, gene co-expression networks, and machine learning algorithms, an RNA modification-related programmed cell death network was constructed, and the pivotal roles of programmed cell death genes in key modules were identified. An RNA modification-related programmed cell death risk score was calculated to predict the occurrence of AD.</p><p><strong>Results: </strong>RPCD-related genes classified patients into subgroups with distinct clinical characteristics. Nineteen key genes were identified and an RPCD risk score was constructed based on the key genes. This score can be used for the diagnosis of AD and the assessment of disease progression in patients. The diagnostic efficacy of the RPCD risk score and the key genes was validated in the ROSMAP, GEO, and ADNI datasets.</p><p><strong>Conclusion: </strong>This study uncovered that RNA modification-related PCD is of significance for AD progression and early prediction, providing insights from a new perspective for the study of disease mechanisms in AD.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"396"},"PeriodicalIF":6.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing innovative machine learning techniques to combat drug resistance in solid tumors.","authors":"Hao Zhang, Wendy Mao","doi":"10.1186/s12967-025-06390-w","DOIUrl":"10.1186/s12967-025-06390-w","url":null,"abstract":"","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"398"},"PeriodicalIF":6.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SOX4 accelerates intervertebral disc degeneration via EZH2/NRF2 pathway in response to mitochondrial ROS-dependent NLRP3 inflammasome activation in nucleus pulposus cells.","authors":"Wenzhi Zhao, Yadong Liu, Yunxiang Hu, Guiqi Zhang","doi":"10.1186/s12967-024-05913-1","DOIUrl":"10.1186/s12967-024-05913-1","url":null,"abstract":"<p><strong>Objective: </strong>The transcription factor SRY-related HMG-box 4 (SOX4) has been implicated in intervertebral disc diseases. This study aimed to investigate the role of SOX4 in intervertebral disc degeneration (IDD) and explore the underlying molecular mechanisms.</p><p><strong>Methods: </strong>We established an IDD rat model via surgery and analyzed SOX4 expression using qRT-PCR and Western blotting. Histological evaluation, immunohistochemistry, and Safranin O staining assessed IDD progression. In vitro, an IDD cellular model was constructed using IL-1β-stimulated nucleus pulposus (NP) cells. SOX4 knockdown and overexpression experiments in NP cells examined SOX4 effects on ECM degradation, NLRP3-mediated pyroptosis, and mitochondrial ROS-dependent NLRP3 inflammasome activation. The involvement of the EZH2/NRF2 pathway in SOX4-mediated NLRP3 activation was also examined.</p><p><strong>Results: </strong>SOX4 expression was significantly increased in IDD rats and promoted IDD progression. Knockdown of SOX4 inhibited ECM degradation and NLRP3-mediated pyroptosis in NP cells. In vitro experiments showed that SOX4 promoted ECM degradation by upregulating MMPs and ADAMTS-5 expression, and suppressed collagen II and aggrecan synthesis. SOX4 knockdown inhibited NLRP3-mediated pyroptosis, while overexpression accelerated it in NP cells. Additionally, SOX4 was found to exacerbate mitochondrial ROS-dependent NLRP3 inflammasome activation in NP cells. Further investigation revealed that SOX4 enhanced NLRP3 inflammasome activation by upregulating EZH2 expression and modulating the EZH2/NRF2 pathway, with EZH2 inhibition attenuating SOX4-induced NLRP3 activation.</p><p><strong>Conclusion: </strong>Our findings suggest that SOX4 accelerates IDD progression by promoting NLRP3 inflammasome activation via modulating the EZH2/NRF2 pathway, leading to NP cell pyroptosis and ECM degradation. Targeting SOX4 may represent a potential therapeutic strategy for treating IDD.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"395"},"PeriodicalIF":6.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene therapy shines light on congenital stationary night blindness for future cures.","authors":"Yi Zhang, Siqi Lin, Lingqi Yu, Xiang Lin, Shuai Qu, Qingyang Ye, Mengting Yu, Wenfeng Chen, Wenjie Wu","doi":"10.1186/s12967-025-06392-8","DOIUrl":"10.1186/s12967-025-06392-8","url":null,"abstract":"<p><p>Congenital Stationary Night Blindness (CSNB) is a non-progressive hereditary eye disease that primarily affects the retinal signal processing, resulting in significantly reduced vision under low-light conditions. CSNB encompasses various subtypes, each with distinct genetic patterns and pathogenic genes. Over the past few decades, gene therapy for retinal genetic disorders has made substantial progress; however, effective clinical therapies for CSNB are yet to be discovered. With the continuous advancement of gene-therapy tools, there is potential for these methods to become effective treatments for CSNB. Nonetheless, challenges remain in the treatment of CSNB, including issues related to delivery vectors, therapeutic efficacy, and possible side effects. This article reviews the clinical diagnosis, pathogenesis, and associated mutated genes of CSNB, discusses existing animal models, and explores the application of gene therapy technologies in retinal genetic disorders, as well as the current state of research on gene therapy for CSNB.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"392"},"PeriodicalIF":6.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"5-Methylcytosine RNA modification and its roles in cancer and cancer chemotherapy resistance.","authors":"Fang Li, Tingting Liu, Yajing Dong, Qianqian Gao, Rongzhu Lu, Zhiyong Deng","doi":"10.1186/s12967-025-06217-8","DOIUrl":"10.1186/s12967-025-06217-8","url":null,"abstract":"<p><p>Recent advancements in cancer therapies have improved clinical outcomes, yet therapeutic resistance remains a significant challenge because of its complex mechanisms. Among epigenetic factors, m5C RNA modification is emerging as a key player in cancer drug resistance, similar to the well-known m6A modification. m5C affects RNA metabolism processes, including splicing, export, translation, and stability, thereby influencing drug efficacy. This review highlights the critical roles of m5C in modulating resistance to chemotherapy, targeted therapy, radiotherapy, and immunotherapy. This review also discusses the functions of key regulators, including methyltransferases, demethylases, and m5C-binding proteins, as essential modulators of the m5C epigenetic landscape that contribute to its dynamic and complex regulatory network. Targeting these regulatory components offers a promising strategy to overcome resistance. We highlight the need for further research to elucidate the specific mechanisms by which m5C contributes to resistance and to develop precise m5C-targeted therapies, presenting m5C-focused strategies as potential novel anticancer treatments.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"390"},"PeriodicalIF":6.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A gene-based predictive model for lymph node metastasis in cervical cancer: superior performance over imaging techniques.","authors":"Dongdong Xu, Xibo Zhao, Dongdong Ye, Chuying Huo, Xuanwei Peng, Yunyun Liu, Huaiwu Lu","doi":"10.1186/s12967-025-06327-3","DOIUrl":"10.1186/s12967-025-06327-3","url":null,"abstract":"<p><strong>Objective: </strong>Lymph node metastasis (LNM) critically impacts the prognosis and treatment decisions of cervical cancer patients. The accuracy and sensitivity of current imaging techniques, such as CT and MRI, are limited in assessing lymph node status. This study aims to develop a more accurate and efficient method for predicting LNM.</p><p><strong>Methods: </strong>Three independent cohorts were merged and divided into training and internal validation groups, with our cohort and those from other centers serving as external validation. A predictive model for LNM in cervical cancer was established using the LASSO regression and multivariate logistic regression. The diagnostic performance of the predictive model was compared with that of CT/MRI in terms of accuracy, sensitivity, specificity, and AUC.</p><p><strong>Results: </strong>Using RNA-seq data, four independent predictive genes (MAPT, EPB41L1, ACSL5, and PRPF4B) were identified through LASSO regression and multivariate logistic regression, and a predictive model was constructed to calculate the LNM risk score. Compared with CT/MRI, the model demonstrated higher diagnostic efficiency, with an accuracy of 0.840 and sensitivity of 0.804, compared to CT/MRI's accuracy of 0.713 and sensitivity of 0.587. The predictive model corrected 81% of misdiagnoses by CT/MRI, demonstrating significant improvements in accuracy and sensitivity.</p><p><strong>Conclusion: </strong>The predictive model developed in this study, based on gene expression data, significantly improves the preoperative assessment accuracy of LNM in cervical cancer. Compared to traditional imaging techniques, this model shows superior sensitivity and accuracy. This study provides a robust foundation for developing precise diagnostic tools, paving the way for future clinical applications in individualized treatment planning.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"397"},"PeriodicalIF":6.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucagon-like Peptide-1 receptor agonists for obstructive sleep apnea in patients with obesity and type 2 diabetes mellitus: a systematic review and meta-analysis.","authors":"Ruifeng Yang, Lindong Zhang, Jiangfan Guo, Ning Wang, Qiue Zhang, Zhiwei Qi, Lili Wu, Lingling Qin, Tonghua Liu","doi":"10.1186/s12967-025-06302-y","DOIUrl":"10.1186/s12967-025-06302-y","url":null,"abstract":"<p><p>The systematic review was registered on the PROSPERO website (CRD42024558287). Our objective is to systematically summarise the clinical evidence of glucagon-like peptide-1 receptor agonists (GLP-1 RA) for obstructive sleep apnea (OSA) in patients with Obesity or/and type 2 Diabetes Mellitus (T2DM). This analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. 10 databases and registers Web of Science, Scopus, PubMed, APA PsycInfo, Embase, Ovid, Cochrane Library, CINAHL, Clinicaltrials.gov, and International Clinical Trials Registry Platform (ICTRP) were retrieved from the establishment to July 14, 2024 for related randomized controlled trials (RCT) and non-RCTs. Data were extracted by two investigators separately, and only the RCTs were included in the quantitative synthesis. The outcome was operated by Review Manager 5.4 and Stata 15.0. Ten studies containing eight RCTs and two non-RCTs were included. The efficacy of the GLP-1 RA group in reducing apnea-hypopnea index (AHI) was superior to that of the control group in patients with T2DM (MD = -5.68, 95%CI [-7.97, -3.38], P < 0.00001, I² = 0%). GLP-1 RAs also possessed a tendency to reduce AHI in patients with obesity but more evidence is needed to support the findings due to the inconsistency. In consideration of the enhanced metabolic parameters observed with GLP-1 RAs, they may be recommended as useful hypoglycaemic medication for the management of T2DM with OSA. Patients with obesity and OSA may consider GLP-1 RA as a potential treatment option if the adverse events are deemed tolerable.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"389"},"PeriodicalIF":6.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11967144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of metagenomics next-generation sequencing on etiological diagnosis and early outcomes in sepsis.","authors":"Feixiang Xu, Chen Chen, Su Lu, Mingming Xue, Hailin Ding, Yanli Song, Yun Zhang, Keyu Sun, Lunxian Tang, Wei Wang, Meitang Wang, Yan Tang, Dingyu Tan, Chenling Yao, Dongwei Shi, Enqiang Mao, Mian Shao, Youguo Ying, Chunmei Zhou, Lihong Huang, Hu Peng, Zhongshu Kuang, Sanqiang Wang, Qingbian Ma, Si Sun, Dongfeng Guo, Tianwen Gu, Bin Yang, Linhao Ma, Chengjin Gao, Xiaoye Lu, Hong Zhang, Ruilan Wang, Chaoyang Tong, Zhenju Song","doi":"10.1186/s12967-025-06332-6","DOIUrl":"10.1186/s12967-025-06332-6","url":null,"abstract":"<p><strong>Background: </strong>Clinical implications of metagenomics next-generation sequencing (mNGS) in sepsis have not been fully evaluated. This study aimed to determine the diagnostic, therapeutic, and prognostic impacts of mNGS in sepsis.</p><p><strong>Methods: </strong>This multicenter prospective study was conducted at 19 sites in China from 2020 to 2021, and 859 adult patients hospitalized with sepsis were enrolled. The advantages, challenges, knowledge gaps and privacy risks of mNGS were carefully introduced to all participants, and participants chose on their own to either receive conventional microbiological test (CMT) alone (conventional-test-only group, n = 394) or receive mNGS test along with CMT (combined test group, n = 465). For prognostic analysis, the primary endpoint was 28-day mortality. Secondary endpoints included 7-day mortality and average per-day hospital cost. Inverse probability of treatment weighting was used to balance covariates between groups. Concurrent CMT and mNGS results from patients in the combined test group were used for diagnostic analyses. Therapeutic impact of mNGS was evaluated based on subsequent antibiotic adjustment.</p><p><strong>Results: </strong>Compared with composite reference standard, the positive percent agreement of mNGS among infected site samples was significantly higher than that of CMT (92.0% [95% CI, 88.7 to 94.5] vs. 51.1% [95% CI, 45.9 to 56.2], p < 0.001), while the negative percent agreement of mNGS was inferior to that of CMT (39.6% [95% CI, 29.5 to 50.4] vs. 69.2% [95% CI, 58.7 to 78.5], p < 0.001). The mNGS test identified causal microbes in 344 (74.0%) patients, and concomitant antibiotic changes occurred in 136 patients (29.2%). Death by day 7 occurred in 24 of 465 (5.2%) patients in the combined test group and in 34 of 394 (8.6%) patients in the conventional-test-only group (hazard ratio, 0.44 [95% CI, 0.26 to 0.77], p = 0.004). However, no significant difference in 28-day mortality was observed between two study groups (hazard ratio, 0.82 [0.56 to 1.20], p = 0.300).</p><p><strong>Conclusions: </strong>The mNGS test of infected site samples exhibited 40% higher pathogen detection rate than CMT in patients with sepsis, which led to improved etiological diagnosis and tailored antibiotic therapy. Additional use of mNGS halved the risk of early death in 7 days, but did not improve 28-day survival in patients with sepsis.</p><p><strong>Trial registration: </strong>chictr.org.cn Identifier: ChiCTR2000031113. Registered 22 March 2020.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"394"},"PeriodicalIF":6.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}