Molecular biomedicine最新文献_第3页

Glycosyltransferase B4GALNT1 promotes immunosuppression in hepatocellular carcinoma via the HES4-SPP1-TAM/Th2 axis. 糖基转移酶B4GALNT1通过HES4-SPP1-TAM/Th2轴促进肝癌的免疫抑制。

IF 6.3

Molecular biomedicine Pub Date : 2024-12-01 DOI: 10.1186/s43556-024-00231-w

Zhifeng Wang, Jiaxin Liu, Xiaoming Wang, Qingyun Wu, Qiao Peng, Tianxiao Yang, Xuehui Sun, Xiaofeng Wang, Yilin Wang, Weicheng Wu

{"title":"Glycosyltransferase B4GALNT1 promotes immunosuppression in hepatocellular carcinoma via the HES4-SPP1-TAM/Th2 axis.","authors":"Zhifeng Wang, Jiaxin Liu, Xiaoming Wang, Qingyun Wu, Qiao Peng, Tianxiao Yang, Xuehui Sun, Xiaofeng Wang, Yilin Wang, Weicheng Wu","doi":"10.1186/s43556-024-00231-w","DOIUrl":"10.1186/s43556-024-00231-w","url":null,"abstract":"β-1,4-N-acetylgalactosaminyltransferase I (B4GALNT1) is a key glycosyltransferase for gangliosides. Its aberrant expression has been observed in various cancers, and its potential roles in tumor immunity were suggested recently. However, how B4GALNT1 regulate tumor progression and tumor immunity remains largely unknown. In this study, we aimed to investigate the roles of B4GALNT1 in hepatocellular carcinoma (HCC), particularly in reshaping the tumor immune microenvironment, and evaluate the potential beneficial effects of targeting B4GALNT1 in immunotherapy. Our data verified the aberrant upregulation of B4GALNT1 in HCC tumor tissues and tumor cells, which could be utilized as an independent prognostic factor and improve the predicting performance of traditional tumor node metastasis (TNM) system. We also demonstrated that B4GALNT1 increased the phosphorylation of Hes Family BHLH Transcription Factor 4 (HES4) via p38 mitogen-activated protein kinase (p38)/ c-Jun N-terminal kinase (JNK) signaling in tumor cells, thus increasing the transcriptional activity of HES4, which upregulated the synthesis and secretion of secreted phosphoprotein 1 (SPP1), modulated the composition of tumor-associated macrophages (TAMs) and T helper type 2 (Th2) cells, and eventually reshaped the immunosuppressive microenvironment. In addition, silencing B4GALNT1 was proved to enhance the tumor-killing efficiency of the programmed cell death protein 1 (PD-1)-targeting strategy in mouse model. In conclusion, this study evaluated B4GALNT1 as a prognostic predictor for HCC patients and revealed the mechanism of B4GALNT1 in microenvironmental remodeling, which extends the understanding of HCC progression and provides a novel auxiliary strategy for HCC immunotherapy.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"65"},"PeriodicalIF":6.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tumor energy metabolism: implications for therapeutic targets. 肿瘤能量代谢：对治疗靶点的影响。

IF 6.3

Molecular biomedicine Pub Date : 2024-11-29 DOI: 10.1186/s43556-024-00229-4

Youwu Hu, Wanqing Liu, WanDi Fang, Yudi Dong, Hong Zhang, Qing Luo

{"title":"Tumor energy metabolism: implications for therapeutic targets.","authors":"Youwu Hu, Wanqing Liu, WanDi Fang, Yudi Dong, Hong Zhang, Qing Luo","doi":"10.1186/s43556-024-00229-4","DOIUrl":"10.1186/s43556-024-00229-4","url":null,"abstract":"Tumor energy metabolism plays a crucial role in the occurrence, progression, and drug resistance of tumors. The study of tumor energy metabolism has gradually become an emerging field of tumor treatment. Recent studies have shown that epigenetic regulation is closely linked to tumor energy metabolism, influencing the metabolic remodeling and biological traits of tumor cells. This review focuses on the primary pathways of tumor energy metabolism and explores therapeutic strategies to target these pathways. It covers key areas such as glycolysis, the Warburg effect, mitochondrial function, oxidative phosphorylation, and the metabolic adaptability of tumors. Additionally, this article examines the role of the epigenetic regulator SWI/SNF complex in tumor metabolism, specifically its interactions with glucose, lipids, and amino acids. Summarizing therapeutic strategies aimed at these metabolic pathways, including inhibitors of glycolysis, mitochondrial-targeted drugs, exploitation of metabolic vulnerabilities, and recent developments related to SWI/SNF complexes as potential targets. The clinical significance, challenges, and future directions of tumor metabolism research are discussed, including strategies to overcome drug resistance, the potential of combination therapy, and the application of new technologies.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"63"},"PeriodicalIF":6.3,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11604893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multidrug resistance in Pseudomonas aeruginosa: genetic control mechanisms and therapeutic advances. 铜绿假单胞菌的多药耐药性：基因控制机制和治疗进展。

IF 6.3

Molecular biomedicine Pub Date : 2024-11-27 DOI: 10.1186/s43556-024-00221-y

Yuanjing Zhao, Haoran Xu, Hui Wang, Ping Wang, Simin Chen

{"title":"Multidrug resistance in Pseudomonas aeruginosa: genetic control mechanisms and therapeutic advances.","authors":"Yuanjing Zhao, Haoran Xu, Hui Wang, Ping Wang, Simin Chen","doi":"10.1186/s43556-024-00221-y","DOIUrl":"10.1186/s43556-024-00221-y","url":null,"abstract":"Pseudomonas aeruginosa is a significant opportunistic pathogen, and its complex mechanisms of antibiotic resistance pose a challenge to modern medicine. This literature review explores the advancements made from 1979 to 2024 in understanding the regulatory networks of antibiotic resistance genes in Pseudomonas aeruginosa, with a particular focus on the molecular underpinnings of these resistance mechanisms. The review highlights four main pathways involved in drug resistance: reducing outer membrane permeability, enhancing active efflux systems, producing antibiotic-inactivating enzymes, and forming biofilms. These pathways are intricately regulated by a combination of genetic regulation, transcriptional regulators, two-component signal transduction, DNA methylation, and small RNA molecules. Through an in-depth analysis and synthesis of existing literature, we identify key regulatory elements mexT, ampR, and argR as potential targets for novel antimicrobial strategies. A profound understanding of the core control nodes of drug resistance offers a new perspective for therapeutic intervention, suggesting that modulating these elements could potentially reverse resistance and restore bacterial susceptibility to antibiotics. The review looks forward to future research directions, proposing the use of gene editing and systems biology to further understand resistance mechanisms and to develop effective antimicrobial strategies against Pseudomonas aeruginosa. This review is expected to provide innovative solutions to the problem of drug resistance in infectious diseases.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"62"},"PeriodicalIF":6.3,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11599538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142735220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Human cytomegalovirus: pathogenesis, prevention, and treatment. 人类巨细胞病毒：发病机制、预防和治疗。

IF 6.3

Molecular biomedicine Pub Date : 2024-11-25 DOI: 10.1186/s43556-024-00226-7

Zifang Shang, Xin Li

{"title":"Human cytomegalovirus: pathogenesis, prevention, and treatment.","authors":"Zifang Shang, Xin Li","doi":"10.1186/s43556-024-00226-7","DOIUrl":"10.1186/s43556-024-00226-7","url":null,"abstract":"Human cytomegalovirus (HCMV) infection remains a significant global health challenge, particularly for immunocompromised individuals and newborns. This comprehensive review synthesizes current knowledge on HCMV pathogenesis, prevention, and treatment strategies. We examine the molecular mechanisms of HCMV entry, focusing on the structure and function of key envelope glycoproteins (gB, gH/gL/gO, gH/gL/pUL128-131) and their interactions with cellular receptors such as PDGFRα, NRP2, and THBD. The review explores HCMV's sophisticated immune evasion strategies, including interference with pattern recognition receptor signaling, modulation of antigen presentation, and regulation of NK and T cell responses. We highlight recent advancements in developing neutralizing antibodies, various vaccine strategies (live-attenuated, subunit, vector-based, DNA, and mRNA), antiviral compounds (both virus-targeted and host-targeted), and emerging cellular therapies such as TCR-T cell approaches. By integrating insights from structural biology, immunology, and clinical research, we identify critical knowledge gaps and propose future research directions. This analysis aims to stimulate cross-disciplinary collaborations and accelerate the development of more effective prevention and treatment strategies for HCMV infections, addressing a significant unmet medical need.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"61"},"PeriodicalIF":6.3,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeted delivery of extracellular vesicles: the mechanisms, techniques and therapeutic applications. 细胞外囊泡的定向输送：机制、技术和治疗应用。

IF 6.3

Molecular biomedicine Pub Date : 2024-11-21 DOI: 10.1186/s43556-024-00230-x

Shuang Zhao, Yunfeng Di, Huilan Fan, Chengyan Xu, Haijing Li, Yong Wang, Wei Wang, Chun Li, Jingyu Wang

{"title":"Targeted delivery of extracellular vesicles: the mechanisms, techniques and therapeutic applications.","authors":"Shuang Zhao, Yunfeng Di, Huilan Fan, Chengyan Xu, Haijing Li, Yong Wang, Wei Wang, Chun Li, Jingyu Wang","doi":"10.1186/s43556-024-00230-x","DOIUrl":"10.1186/s43556-024-00230-x","url":null,"abstract":"Extracellular vesicles (EVs) are cell-derived vesicles with a phospholipid bilayer measuring 50-150 nm in diameter with demonstrated therapeutic potentials. Limitations such as the natural biodistribution (mainly concentrated in the liver and spleen) and short plasma half-life of EVs present significant challenges to their clinical translation. In recent years, growing research indicated that engineered EVs with enhanced targeting to lesion sites have markedly promoted therapeutic efficacy. However, there is a dearth of systematic knowledge on the recent advances in engineering EVs for targeted delivery. Herein, we provide an overview of the targeting mechanisms, engineering techniques, and clinical translations of natural and engineered EVs in therapeutic applications. Enrichment of EVs at lesion sites may be achieved through the recognition of tissue markers, pathological changes, and the circumvention of mononuclear phagocyte system (MPS). Alternatively, external stimuli, including magnetic fields and ultrasound, may also be employed. EV engineering techniques that fulfill targeting functions includes genetic engineering, membrane fusion, chemical modification and physical modification. A comparative statistical analysis was conducted to elucidate the discrepancies between the diverse techniques on size, morphology, stability, targeting and therapeutic efficacy in vitro and in vivo. Additionally, a summary of the registered clinical trials utilizing EVs from 2010 to 2023 has been provided, with a full discussion on the perspectives. This review provides a comprehensive overview of the mechanisms and techniques associated with targeted delivery of EVs in therapeutic applications to advocate further explorations of engineered EVs and accelerate their clinical applications.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"60"},"PeriodicalIF":6.3,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11579273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unveiling the role of Pleckstrin-2 in tumor progression and immune modulation: insights from a comprehensive pan-cancer analysis with focus on lung cancer. 揭示 Pleckstrin-2 在肿瘤进展和免疫调节中的作用：以肺癌为重点的泛癌症综合分析的启示。

IF 6.3

Molecular biomedicine Pub Date : 2024-11-15 DOI: 10.1186/s43556-024-00225-8

Enzhi Yin, Chengming Liu, Yuxin Yao, Yuejun Luo, Yaning Yang, Xiaoya Tang, Sufei Zheng, Linyan Tian, Jie He

{"title":"Unveiling the role of Pleckstrin-2 in tumor progression and immune modulation: insights from a comprehensive pan-cancer analysis with focus on lung cancer.","authors":"Enzhi Yin, Chengming Liu, Yuxin Yao, Yuejun Luo, Yaning Yang, Xiaoya Tang, Sufei Zheng, Linyan Tian, Jie He","doi":"10.1186/s43556-024-00225-8","DOIUrl":"10.1186/s43556-024-00225-8","url":null,"abstract":"Cancer remains a leading cause of mortality globally, highlighting the need for novel biomarkers to enhance prognosis and therapeutic strategies. Pleckstrin-2 (PLEK2), a member of the pleckstrin family, has been implicated in processes critical to tumor progression, but its role across cancers remains underexplored. This study systematically examined the expression patterns, prognostic relevance, and functional impact of PLEK2 across multiple cancer types. Using data from The Cancer Genome Atlas (TCGA), Genotype Tissue Expression Project (GTEx), and the Human Protein Atlas, we analyzed PLEK2 expression in both cancerous and normal tissues, revealing significant overexpression of PLEK2 in various cancers at the mRNA and protein levels. Single-cell RNA sequencing further indicated predominant expression of PLEK2 in tumor cells and macrophages within the tumor microenvironment. Survival analysis demonstrated that elevated PLEK2 expression correlated with poor prognosis in specific cancers, though its impact varied across cancer types. Functional assays showed that PLEK2 knockdown inhibited proliferation and migration in human cancer cell lines. In vivo studies using a Lewis lung carcinoma (LLC) model confirmed that PLEK2 knockdown suppressed tumor growth and enhanced the efficacy of PD-1 immunotherapy. Mechanistically, PLEK2 knockdown was associated with reduced AKT pathway activation, diminished tumor-associated macrophage infiltration, and increased CD8 T cell presence. Compounds like Navitoclax were also identified as potential PLEK2 inhibitors. In conclusion, PLEK2 played a multifaceted role in cancer progression and immune response modulation. Targeting PLEK2 might suppress tumor growth and overcome immunotherapy resistance, offering a promising biomarker and therapeutic target to improve cancer treatment outcomes.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"59"},"PeriodicalIF":6.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

XAF1 antagonizes TRIM28 activity through the assembly of a ZNF313-mediated destruction complex to suppress tumor malignancy. XAF1 通过组装 ZNF313 介导的破坏复合物来拮抗 TRIM28 的活性，从而抑制肿瘤的恶性发展。

IF 6.3

Molecular biomedicine Pub Date : 2024-11-13 DOI: 10.1186/s43556-024-00224-9

Seung-Hun Jang, Hwi-Wan Choi, Jieun Ahn, Sungchan Jang, Ji-Hye Yoon, Min-Goo Lee, Sung-Gil Chi

{"title":"XAF1 antagonizes TRIM28 activity through the assembly of a ZNF313-mediated destruction complex to suppress tumor malignancy.","authors":"Seung-Hun Jang, Hwi-Wan Choi, Jieun Ahn, Sungchan Jang, Ji-Hye Yoon, Min-Goo Lee, Sung-Gil Chi","doi":"10.1186/s43556-024-00224-9","DOIUrl":"10.1186/s43556-024-00224-9","url":null,"abstract":"X-linked inhibitor of apoptosis-associated factor 1 (XAF1) is a stress-inducible pro-apoptotic protein that is commonly inactivated in multiple human cancers. Nevertheless, the molecular basis for its tumor suppression function remains largely uncharacterized. Here we report that XAF1 antagonizes the oncogenic activity of tripartite motif containing 28 (TRIM28) ubiquitin E3 ligase through zinc finger protein 313 (ZNF313)-induced ubiquitination and proteasomal degradation. XAF1 exerts apoptosis-promoting effect more strongly in TRIM28+/+ versus XAF1-/- tumor cells and suppresses tumor cell growth, migration, invasion, and epithelial-to-mesenchymal transition and xenograft tumor growth in a highly TRIM28-dependent fashion. Mechanistically, XAF1 interacts directly with the RING domains of TRIM28 and ZNF313 through the ZF6 and ZF7 domain, respectively, thereby facilitating ZNF313 interaction with and ubiquitination of TRIM28. A mutant XAF1 lacking either ZF6 or ZF7 domain exhibits no activity to promote TRIM28 ubiquitination. By destabilizing TRIM28, XAF1 blocks TRIM28-driven ubiquitination of p53 and RLIM, p53-HDAC1 interaction, and TWIST1 stabilization. Intriguingly, TRIM28 destabilizes XAF1 through K48-linked polyubiquitination and proteasomal degradation to protect tumor cells from apoptotic stress, indicating its role as an intrinsic antagonist against XAF1 and the antagonistic interplay of XAF1 and TRIM28. XAF1 expression is inversely correlated with TRIM28 expression in cancer cell lines and tumor tissues and more tightly associated with the survival of TRIM28-high versus TRIM28-low patients. Together, this study uncovers a novel mechanism by which XAF1 suppresses tumor malignancy and an important role for XAF1-TRIM28 interplay in governing stress response, illuminating the mechanistic consequence of its alteration during tumorigenic process.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"58"},"PeriodicalIF":6.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Proteogenomics identifies c-Met inhibition as a therapeutic strategy for BAP1-deficient clear cell renal cell carcinoma. 蛋白质基因组学发现 c-Met 抑制是治疗 BAP1 缺陷透明细胞肾细胞癌的一种策略。

IF 6.3

Molecular biomedicine Pub Date : 2024-11-12 DOI: 10.1186/s43556-024-00220-z

Bowen Du, Yulin Zhou, Wenzhi Li, Haowei He, Ming Chen, Ninghan Feng

引用次数: 0

Prophylactic and therapeutic vaccine development: advancements and challenges. 预防性和治疗性疫苗开发：进步与挑战。

IF 6.3

Molecular biomedicine Pub Date : 2024-11-11 DOI: 10.1186/s43556-024-00222-x

Induni Nayodhara Weerarathna, Elijah Skarlus Doelakeh, Lydia Kiwanuka, Praveen Kumar, Sanvi Arora

{"title":"Prophylactic and therapeutic vaccine development: advancements and challenges.","authors":"Induni Nayodhara Weerarathna, Elijah Skarlus Doelakeh, Lydia Kiwanuka, Praveen Kumar, Sanvi Arora","doi":"10.1186/s43556-024-00222-x","DOIUrl":"10.1186/s43556-024-00222-x","url":null,"abstract":"Biomedical research is fundamental in developing preventive and therapeutic vaccines, serving as a cornerstone of global public health. This review explores the key concepts, methodologies, tools, and challenges in the vaccine development landscape, focusing on transitioning from basic biomedical sciences to clinical applications. Foundational disciplines such as virology, immunology, and molecular biology lay the groundwork for vaccine creation, while recent innovations like messenger RNA (mRNA) technology and reverse vaccinology have transformed the field. Additionally, it highlights the role of pharmaceutical advancements in translating lab discoveries into clinical solutions. Techniques like CRISPR-Cas9, genome sequencing, monoclonal antibodies, and computational modeling have significantly enhanced vaccine precision and efficacy, expediting the development of vaccines against infectious diseases. The review also discusses challenges that continue to hinder progress, including stringent regulatory pathways, vaccine hesitancy, and the rapid emergence of new pathogens. These obstacles underscore the need for interdisciplinary collaboration and the adoption of innovative strategies. Integrating personalized medicine, nanotechnology, and artificial intelligence is expected to revolutionize vaccine science further. By embracing these advancements, biomedical research has the potential to overcome existing challenges and usher in a new era of therapeutic and prophylactic vaccines, ultimately improving global health outcomes. This review emphasizes the critical role of vaccines in combating current and future health threats, advocating for continued investment in biomedical science and technology.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"57"},"PeriodicalIF":6.3,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cervicovaginal lavages uncover growth factors as key biomarkers for early diagnosis and prognosis of endometrial cancer. 宫颈阴道灌洗发现生长因子是早期诊断和预后子宫内膜癌的关键生物标志物。

IF 5.3

Molecular biomedicine Pub Date : 2024-11-08 DOI: 10.1186/s43556-024-00219-6

Hannah J Harris, Paweł Łaniewski, Haiyan Cui, Denise J Roe, Dana M Chase, Melissa M Herbst-Kralovetz

{"title":"Cervicovaginal lavages uncover growth factors as key biomarkers for early diagnosis and prognosis of endometrial cancer.","authors":"Hannah J Harris, Paweł Łaniewski, Haiyan Cui, Denise J Roe, Dana M Chase, Melissa M Herbst-Kralovetz","doi":"10.1186/s43556-024-00219-6","DOIUrl":"10.1186/s43556-024-00219-6","url":null,"abstract":"Endometrial cancer (EC) rates are continuing to rise and it remains the most common gynecologic cancer in the US. Existing diagnostic methods are invasive and can cause pain and anxiety. Hence, there is a need for less invasive diagnostics for early EC detection. The study objective was to evaluate the utility of growth factors collected through minimally invasive cervicovaginal lavage (CVL) sampling as diagnostic and prognostic biomarkers for EC. CVL samples from 192 individuals undergoing hysterectomy for benign or malignant conditions were collected and used to quantify the concentrations of 19 growth and angiogenic factors using multiplex immunoassays. Patients were categorized based on disease groups: benign conditions (n = 108), endometrial hyperplasia (n = 18), and EC (n = 66). EC group was stratified into grade 1/2 endometrial endometrioid cancer (n = 53) and other EC subtypes (n = 13). Statistical associations were assessed using receiver operating characteristics, Spearman correlations and hierarchical clustering. Growth and angiogenic factors: angiopoietin-2, endoglin, fibroblast activation protein (FAP), melanoma inhibitory activity, and vascular endothelial growth factor-A (VEGF-A) were significantly (p < 0.0001) elevated in EC patients. A multivariate model combining 11 proteins with patient age and body mass index exhibited excellent discriminatory potential (area under curve = 0.918) for EC, with a specificity of 90.7% and a sensitivity of 87.8%. Moreover, angiopoietin-2, FAP and VEGF-A significantly (p < 0.05-0.001) associated with tumor grade, size, myometrial invasion, and mismatch repair status. Our results highlight the innovative use of growth and angiogenic factors collected through CVL sampling for the detecting endometrial cancer, showcasing not only their diagnostic potential but also their prognostic value.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"55"},"PeriodicalIF":5.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0