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Transcriptomic analysis of transformed small-cell lung cancer from EGFR-mutated lung adenocarcinoma reveals distinct subgroups and precision therapy opportunities. egfr突变肺腺癌转化小细胞肺癌的转录组学分析揭示了不同的亚组和精确治疗机会。
IF 9.5 2区 医学
Biomarker Research Pub Date : 2025-05-28 DOI: 10.1186/s40364-025-00789-9
Hao Sun, Chan-Yuan Zhang, Xiu-Hao Zhang, Zai-Xian Tai, Jun-Wei Su, Xiao-Cheng Lin, Shi-Ling Zhang, Yu-Fa Li, Chao Zhang, Miao Cai, Xu-Chao Zhang, Hua-Jun Chen, Qing Zhou, Yi-Long Wu, Wei-Neng Feng, Jin-Ji Yang
{"title":"Transcriptomic analysis of transformed small-cell lung cancer from EGFR-mutated lung adenocarcinoma reveals distinct subgroups and precision therapy opportunities.","authors":"Hao Sun, Chan-Yuan Zhang, Xiu-Hao Zhang, Zai-Xian Tai, Jun-Wei Su, Xiao-Cheng Lin, Shi-Ling Zhang, Yu-Fa Li, Chao Zhang, Miao Cai, Xu-Chao Zhang, Hua-Jun Chen, Qing Zhou, Yi-Long Wu, Wei-Neng Feng, Jin-Ji Yang","doi":"10.1186/s40364-025-00789-9","DOIUrl":"10.1186/s40364-025-00789-9","url":null,"abstract":"<p><strong>Background: </strong>Small-cell lung cancer (SCLC) transformation is one of the major mechanisms of resistance to Epidermal Growth Factor Receptor tyrosine kinase inhibitors (EGFR-TKIs). Chemotherapy is typically the recommended treatment for transformed SCLC (T-SCLC), similar to primary SCLC. However, the benefits of chemotherapy alone are minimal. Prior research highlights differences between the biological traits of T-SCLC and primary SCLC or EGFR-mutated lung adenocarcinoma (LUAD). This study aims to elucidate the molecular characteristics of T-SCLC and identify potential treatment modalities.</p><p><strong>Methods: </strong>We retrospectively collected tissue samples from LUAD, T-SCLC post-EGFR-TKI resistance, and primary SCLC. Genomics, transcriptomics, and proteomics were performed to clarify the differences between T-SCLC, LUAD, and primary SCLC. Hierarchical clustering analysis was then used to categorize the molecular subtype of T-SCLC, followed by a survival analysis based on these subtypes.</p><p><strong>Results: </strong>A study involving 61 patients investigated differences between LUAD, SCLC, and primary SCLC. RNA sequencing revealed distinct gene expression variations, particularly up-regulation in PPM1E, INSM1, and KCNC1 genes in T-SCLC. Pathway analysis linked T-SCLC to the cell cycle and neural differentiation. By conducting Hierarchical clustering analysis on RNA-seq data, the entire population can be categorized into two distinct groups. While certain T-SCLC showed similarities and differences compared to SCLC, with subtypes: LUAD-like and Non-LUAD-like. Notably, the LUAD-like subtype had significantly higher NKX2-1 expression (mean 371.8 vs. 41.8, P < 0.0001). T-SCLC treatment approaches were categorized into matched and unmatched groups, delineated by the alignment of specific therapies with corresponding pathologies. The matched group (13 cases) exhibited a significantly prolonged median progression-free survival compared to the unmatched group (10 cases) (5.4 months vs. 3.6 months, P = 0.02).</p><p><strong>Conclusions: </strong>T-SCLC exhibits marked molecular distinctiveness, setting it apart not only from LUAD but also from classical SCLC. This distinction extends to its classification into two discernible molecular subtypes: LUAD-like and Non-LUAD-like. Customizing therapeutic protocols to align with these specific subtypes have the potential to identify the most appropriate treatment for T-SCLC.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"79"},"PeriodicalIF":9.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175553","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}
引用次数: 0
Extracellular matrix: unlocking new avenues in cancer treatment. 细胞外基质:开启癌症治疗的新途径。
IF 9.5 2区 医学
Biomarker Research Pub Date : 2025-05-27 DOI: 10.1186/s40364-025-00757-3
Jia Jing Lee, Khuen Yen Ng, Athirah Bakhtiar
{"title":"Extracellular matrix: unlocking new avenues in cancer treatment.","authors":"Jia Jing Lee, Khuen Yen Ng, Athirah Bakhtiar","doi":"10.1186/s40364-025-00757-3","DOIUrl":"10.1186/s40364-025-00757-3","url":null,"abstract":"<p><p>The extracellular matrix (ECM) plays a critical role in cancer progression by influencing tumor growth, invasion, and metastasis. This review explores the emerging therapeutic strategies that target the ECM as a novel approach in cancer treatment. By disrupting the structural and biochemical interactions within the tumor microenvironment, ECM-targeted therapies aim to inhibit cancer progression and overcome therapeutic resistance. We examine the current state of ECM research, focusing on key components such as collagen, laminin, fibronectin, periostin, and hyaluronic acid, and their roles in tumor biology. Additionally, we discuss the challenges associated with ECM-targeted therapies, including drug delivery, specificity, and potential side effects, while highlighting recent advancements and future directions. This review underscores the potential of ECM-focused strategies to enhance the efficacy of existing treatments and contribute to more effective cancer therapies.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"78"},"PeriodicalIF":9.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163701","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}
引用次数: 0
Single cell analysis identified IFN signaling activation contributes to the pathogenesis of pediatric steroid-sensitive nephrotic syndrome. 单细胞分析确定IFN信号激活有助于儿童类固醇敏感性肾病综合征的发病机制。
IF 9.5 2区 医学
Biomarker Research Pub Date : 2025-05-24 DOI: 10.1186/s40364-025-00790-2
Qiu-Yu Li, Fei Liu, Xiaoyi Li, Minchao Kang, Linnan Bai, Tong Tong, Chen Zheng, Yanyan Jin, Xiaojing Zhang, Yi Xie, Dandan Tian, Yuanqing Pan, Jingjing Wang, Haidong Fu, Na Jiao, Junnan Wu, JianHua Mao
{"title":"Single cell analysis identified IFN signaling activation contributes to the pathogenesis of pediatric steroid-sensitive nephrotic syndrome.","authors":"Qiu-Yu Li, Fei Liu, Xiaoyi Li, Minchao Kang, Linnan Bai, Tong Tong, Chen Zheng, Yanyan Jin, Xiaojing Zhang, Yi Xie, Dandan Tian, Yuanqing Pan, Jingjing Wang, Haidong Fu, Na Jiao, Junnan Wu, JianHua Mao","doi":"10.1186/s40364-025-00790-2","DOIUrl":"10.1186/s40364-025-00790-2","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic nephrotic syndrome (INS) is a prevalent condition whose recurrence leads to multiple adverse effects. Previous studies on INS pathogenesis primarily focused on immune dysregulation, particularly T-cell changes and their correlation with cytokine shifts. Accumulating evidence suggests that B-cell dysfunction also plays a role. Nevertheless, a comprehensive understanding of the mechanisms and effective treatment strategies remains incomplete.</p><p><strong>Methods: </strong>This study investigates changes in gene expressions and cellular interactions of immune cells at a single-cell level using peripheral blood mononuclear cells (PBMCs). And subsequently validated through quantitative PCR (qPCR), enzyme-linked immunosorbent assay (ELISA), and flow cytometry.</p><p><strong>Results: </strong>We identified seven main clusters using unsupervised clustering of 103,213 high-quality single cells. Through unsupervised clustering, patient-specific T cells (IFI44L + CD4 + T cells) that exhibited a pronounced elevation of interferon-stimulated genes (ISGs) is identified. Activation of ISGs and interferon (IFN)-related pathways are also observed in other clusters. Specifically, this study demonstrates that interferon-γ (IFN-γ) plays a crucial role by promoting the interaction between B-cell activating factor (BAFF) and receptors on B cells. This interaction triggers the release of autoantibodies, thereby initiating INS pathogenesis. Furthermore, telitacicept has shown efficacy in treating pediatric patients with frequent relapse NS(FRNS).</p><p><strong>Conclusions: </strong>Overall, our findings underscore the role of interferon and its related pathways in INS pathogenesis, providing novel therapeutic interventions for NS.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"77"},"PeriodicalIF":9.5,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144288","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}
引用次数: 0
Early kinetics of serum amyloid A predict clinical benefit to first-line chemoimmunotherapy and immunotherapy in advanced non-small cell lung cancer: a retrospective analysis. 血清淀粉样蛋白A的早期动力学预测一线化疗免疫治疗和晚期非小细胞肺癌免疫治疗的临床获益:回顾性分析。
IF 9.5 2区 医学
Biomarker Research Pub Date : 2025-05-24 DOI: 10.1186/s40364-025-00791-1
Wei Du, Jianhua Zhan, Kai Wu, Yanming Wang, Li Zhang, Shaodong Hong
{"title":"Early kinetics of serum amyloid A predict clinical benefit to first-line chemoimmunotherapy and immunotherapy in advanced non-small cell lung cancer: a retrospective analysis.","authors":"Wei Du, Jianhua Zhan, Kai Wu, Yanming Wang, Li Zhang, Shaodong Hong","doi":"10.1186/s40364-025-00791-1","DOIUrl":"10.1186/s40364-025-00791-1","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for advanced non-small cell lung cancer (NSCLC), yet durable responses remain limited in a subset of patients. Serum amyloid A (SAA), an acute-phase protein linked to systemic inflammation, may reflect dynamic immune responses. This retrospective study analyzed 242 advanced NSCLC patients treated with first-line chemoimmunotherapy or immunotherapy between August 2016 and December 2024. Patients were stratified by early SAA kinetics into flare-responders (initial rise followed by decline), responders (sustained decline), and non-responders. Clinical outcomes, including progression-free survival (PFS) and overall survival (OS), were evaluated using Kaplan-Meier and Cox regression analyses. In the chemoimmunotherapy cohort, SAA flare-responders demonstrated significantly prolonged median PFS (29.8 months, 95% CI: 9.95-49.65; HR: 0.31, 95% CI: 0.15-0.64; p < 0.01) compared to non-responders (7.4 months, 95% CI: 4.67-10.13). Similarly, in the immunotherapy cohort, SAA flare-responders showed superior PFS. (19.9 vs. 2.1 months, HR 0.31, p < 0.01). Multivariate analysis confirmed early SAA kinetics as an independent prognostic factor for both PFS and OS in both treatment groups. Early SAA kinetics serve as a promising non-invasive biomarker for predicting clinical outcomes in advanced NSCLC treated with first-line chemoimmunotherapy or immunotherapy. These findings highlight SAA kinetics as a potential non-invasive biomarker and monitoring SAA dynamics may aid in identifying patients with higher likelihood of clinical benefit; however, prospective studies are required to determine its utility in guiding therapeutic decisions.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"76"},"PeriodicalIF":9.5,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132047","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}
引用次数: 0
The progress and prospects of targeting the adenosine pathway in cancer immunotherapy. 靶向腺苷途径在肿瘤免疫治疗中的进展与展望。
IF 9.5 2区 医学
Biomarker Research Pub Date : 2025-05-19 DOI: 10.1186/s40364-025-00784-0
Yuying Yang, Lin Zhu, Yantao Xu, Long Liang, Li Liu, Xiang Chen, Hui Li, Hong Liu
{"title":"The progress and prospects of targeting the adenosine pathway in cancer immunotherapy.","authors":"Yuying Yang, Lin Zhu, Yantao Xu, Long Liang, Li Liu, Xiang Chen, Hui Li, Hong Liu","doi":"10.1186/s40364-025-00784-0","DOIUrl":"10.1186/s40364-025-00784-0","url":null,"abstract":"<p><p>Despite the notable success of cancer immunotherapy, its effectiveness is often limited in a significant proportion of patients, highlighting the need to explore alternative tumor immune evasion mechanisms. Adenosine, a key metabolite accumulating in hypoxic tumor regions, has emerged as a promising target in oncology. Inhibiting the adenosinergic pathway not only inhibits tumor progression but also holds potential to enhance immunotherapy outcomes. Multiple therapeutic strategies targeting this pathway are being explored, ranging from preclinical studies to clinical trials. This review examines the complex interactions between adenosine, its receptors, and the tumor microenvironment, proposing strategies to target the adenosinergic axis to boost anti-tumor immunity. It also evaluates early clinical data on pharmacological inhibitors of the adenosinergic pathway and discusses future directions for improving clinical responses.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"75"},"PeriodicalIF":9.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103166","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}
引用次数: 0
A plasma 9-microRNA signature for lung cancer early detection: a multicenter analysis. 肺癌早期检测的血浆9-microRNA信号:多中心分析
IF 9.5 2区 医学
Biomarker Research Pub Date : 2025-05-16 DOI: 10.1186/s40364-025-00787-x
Elisa Dama, Tommaso Colangelo, Roberto Cuttano, Rafal Dziadziuszko, Thomas Dandekar, Piotr Widlak, Witold Rzyman, Giulia Veronesi, Fabrizio Bianchi
{"title":"A plasma 9-microRNA signature for lung cancer early detection: a multicenter analysis.","authors":"Elisa Dama, Tommaso Colangelo, Roberto Cuttano, Rafal Dziadziuszko, Thomas Dandekar, Piotr Widlak, Witold Rzyman, Giulia Veronesi, Fabrizio Bianchi","doi":"10.1186/s40364-025-00787-x","DOIUrl":"10.1186/s40364-025-00787-x","url":null,"abstract":"<p><p>Lung cancer remains the leading cause of cancer-related deaths worldwide. Low-dose computed tomography (LD-CT) screening, combined with effective minimally invasive molecular testing such circulating microRNA, has the potential to reduce the burden of lung cancer. However, their clinical application requires further validation, including studies across diverse patient cohorts from different countries. In this study, we propose a signature of 9 circulating miRNAs derived from a robust multi-platform workflow with a multi-center design, for a total of 276 lung cancer and 451 non-cancer controls, based on the data from two European LD-CT screening cohorts (Poland and Italy). The classification performance of the signature was stable in the two screening cohorts, with AUC=0.78 (SE, 76%; SP, 67%; ACC=70%), and AUC=0.75 (SE, 82%; SP, 68%; ACC=71%) in the Polish and Italian cohorts, respectively. The diagnostic accuracy of the signature was remarkably independent of age, gender, smoking (status and intensity), nodule size, and density. Additionally, the signature demonstrated strong performance in detecting stage I lung cancer, with AUC=0.76 (95%CI: 0.68-0.84), and 0.69 (95%CI: 0.49-0.89) in the Polish and Italian cohorts respectively, with a prediction ability of 63-73%. The signature's ability to discriminate benign nodules was satisfactory, with AUC=0.71 (95%CI: 0.58-0.84). The proposed panel of 9 circulating miRNAs provides a robust and precise diagnostic tool to substantially advance the effectiveness of the LD-CT screening program.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"74"},"PeriodicalIF":9.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086934","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}
引用次数: 0
Insights into KMT2A rearrangements in acute myeloid leukemia: from molecular characteristics to targeted therapies. 急性髓系白血病中KMT2A重排的研究:从分子特征到靶向治疗
IF 9.5 2区 医学
Biomarker Research Pub Date : 2025-05-13 DOI: 10.1186/s40364-025-00786-y
Sara Zehtabcheh, Hamed Soleimani Samarkhazan, Marjan Asadi, Mitra Zabihi, Sahar Parkhideh, Mohammad Hossein Mohammadi
{"title":"Insights into KMT2A rearrangements in acute myeloid leukemia: from molecular characteristics to targeted therapies.","authors":"Sara Zehtabcheh, Hamed Soleimani Samarkhazan, Marjan Asadi, Mitra Zabihi, Sahar Parkhideh, Mohammad Hossein Mohammadi","doi":"10.1186/s40364-025-00786-y","DOIUrl":"10.1186/s40364-025-00786-y","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) with KMT2A rearrangements (KMT2A-r) represents a highly aggressive and prognostically unfavorable subtype of leukemia, often resistant to standard treatments and associated with high relapse rates. KMT2A-r, found in 3-10% of adult AML cases, disrupt epigenetic regulation by forming chimeric proteins that activate oncogenic pathways like HOXA and MEIS1. These fusion proteins recruit cofactors such as Menin and DOT1L, driving leukemogenesis through abnormal histone methylation. Diagnosing KMT2A-r AML requires precision, with traditional methods like FISH and RT-PCR being complemented by advanced technologies such as next-generation sequencing (NGS) and machine learning (ML). ML models, leveraging transcriptomic data, can predict KMT2A-r and identify biomarkers like LAMP5 and SKIDA1, improving risk stratification. Therapeutically, there is a shift from chemotherapy to targeted therapies. Menin inhibitors (e.g., Revumenib, Ziftomenib) disrupt the Menin-KMT2A interaction, suppressing HOXA/MEIS1 and promoting differentiation. DOT1L inhibitors (e.g., Pinometostat) show promise in combination therapies, while novel approaches like WDR5 inhibitors and PROTAC-mediated degradation are expanding treatment options. Despite progress, challenges remain, including optimizing minimal residual disease monitoring, overcoming resistance, and validating biomarkers. This review emphasizes the imperative to translate molecular insights into personalized therapeutic regimens, offering renewed hope for patients afflicted by this historically refractory malignancy.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"73"},"PeriodicalIF":9.5,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065092","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}
引用次数: 0
S100A9 as a potential novel target for experimental autoimmune cystitis and interstitial cystitis/bladder pain syndrome. S100A9作为实验性自身免疫性膀胱炎和间质性膀胱炎/膀胱痛综合征的潜在新靶点
IF 9.5 2区 医学
Biomarker Research Pub Date : 2025-05-09 DOI: 10.1186/s40364-025-00763-5
Jiang Zhao, Mi Zhou, Chengfei Yang, Yang-Wuyue Liu, Teng Yang, Bishao Sun, Benyi Li, Ji Zheng, Shuangshuang Dai, Zhenxing Yang, Xiangwei Wang
{"title":"S100A9 as a potential novel target for experimental autoimmune cystitis and interstitial cystitis/bladder pain syndrome.","authors":"Jiang Zhao, Mi Zhou, Chengfei Yang, Yang-Wuyue Liu, Teng Yang, Bishao Sun, Benyi Li, Ji Zheng, Shuangshuang Dai, Zhenxing Yang, Xiangwei Wang","doi":"10.1186/s40364-025-00763-5","DOIUrl":"https://doi.org/10.1186/s40364-025-00763-5","url":null,"abstract":"<p><strong>Background: </strong>Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory disease of the bladder for which no effective therapy is currently available. Understanding the pathogenesis of IC/BPS and identifying effective intervention targets are of great clinical importance for its effective treatment. Our work focuses on elucidating the key targets and underlying mechanisms of IC/BPS.</p><p><strong>Methods: </strong>We established an experimental autoimmune cystitis (EAC) mouse model and generated gene knockout mice to elucidate key mediators triggering chronic inflammatory damage in IC/BPS through using single-cell RNA sequencing, proteomic sequencing, and molecular biology experiments.</p><p><strong>Results: </strong>Our study revealed that the infiltration and activation of macrophages, T cells, and mast cells exacerbated inflammatory bladder damage in both IC/BPS and EAC mice. Notably, cell-cell communication among bladder immune cells was significantly enhanced in EAC mice. Macrophages, as the main cell types altered in EAC mice, received and transmitted the most intensity signalling. Mechanistically, macrophages synthesized and secreted S100A9, which in turn facilitated macrophage polarization and promoted the production of pro-inflammatory cytokines. S100A9 emerged as an important pro-inflammatory and pathogenic molecule in IC/BPS and EAC. Further analysis demonstrated that S100A9 activation enhanced the inflammatory response and exacerbated bladder tissue damage in IC/BPS patients and EAC mice via TLR4/NF-κB and TLR4/p38 signalling pathways. Importantly, inhibition of S100A9 with paquinimod, as well as genetic knockout of S100A9, significantly attenuated the pathological process.</p><p><strong>Conclusions: </strong>S100A9 is an important pro-inflammatory and pathogenic molecule in IC/BPS and EAC. Targeting S100A9-initiated signalling pathways may offer a novel therapeutic strategy for IC/BPS.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"72"},"PeriodicalIF":9.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055747","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}
引用次数: 0
Reliable detection of CNS lymphoma-derived circulating tumor DNA in cerebrospinal fluid using multi-biomarker NGS profiling: insights from a real-world study. 使用多生物标志物NGS分析可靠地检测脑脊液中CNS淋巴瘤来源的循环肿瘤DNA:来自现实世界研究的见解
IF 9.5 2区 医学
Biomarker Research Pub Date : 2025-05-09 DOI: 10.1186/s40364-025-00777-z
Veronika Navrkalova, Andrea Mareckova, Samuel Hricko, Viera Hrabcakova, Lenka Radova, Vaclav Kubes, Jakub Porc, Tomas Reigl, Sarka Pospisilova, Jana Kotaskova, Andrea Janikova
{"title":"Reliable detection of CNS lymphoma-derived circulating tumor DNA in cerebrospinal fluid using multi-biomarker NGS profiling: insights from a real-world study.","authors":"Veronika Navrkalova, Andrea Mareckova, Samuel Hricko, Viera Hrabcakova, Lenka Radova, Vaclav Kubes, Jakub Porc, Tomas Reigl, Sarka Pospisilova, Jana Kotaskova, Andrea Janikova","doi":"10.1186/s40364-025-00777-z","DOIUrl":"https://doi.org/10.1186/s40364-025-00777-z","url":null,"abstract":"<p><strong>Background: </strong>Diagnosing primary or secondary CNS lymphoma (CNSL) is a clinical challenge due to the limitations of standard biopsy and imaging procedures despite established guidelines. Therefore, accurate biomarkers and analytical methods that are convenient for practical routine use are needed to diagnose and manage these aggressive lymphomas effectively. We evaluated the utility of minimally invasive circulating tumor DNA (ctDNA) detection in a prospective real-world scenario, moving this approach closer to clinical practice.</p><p><strong>Methods: </strong>A total of 164 plasma, cerebrospinal fluid (CSF), and tumor samples from 56 CNSL patients were collected to analyze tumor DNA by the diagnostic next-generation sequencing (NGS) panel LYNX, enabling simultaneous analysis of gene variants, chromosomal aberrations, and antigen receptor rearrangements in targeted regions.</p><p><strong>Results: </strong>The well-known genetic heterogeneity of CNSL was refined with integrative molecular data, showing the most frequent MYD88, PIM1, and KMT2D mutations and a broad spectrum of chromosomal aberrations, reflecting high genomic complexity. The multi-target approach achieved a substantially higher detection rate of CNS infiltration (90%) than tracking a single variant in gene MYD88 (46%). CSF clearly surpasses plasma if applying a routine (non-ultrasensitive) NGS approach and allows for more reliable evidence of CNS involvement than conventional flow cytometry (91% vs. 21%, p < 0.001). Parallel analysis of tumor DNA in both cell-free and cellular DNA from CSF makes the probability of primary or secondary CNS malignancy detection even higher.</p><p><strong>Conclusions: </strong>Our prospective, tissue-agnostic approach highlights the feasibility of ctDNA sequencing by a commonplace and affordable method, offering higher sensitivity to detect CNS infiltration with lymphoma than standard cell-analyzing techniques. We accentuate the benefit of a multi-target NGS approach and adequate CSF sampling to obtain satisfactory diagnostic yield. Less invasive liquid biopsy testing by comprehensive NGS complements standard procedures in the diagnostics and management of CNSL patients, especially when encountering limitations.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"71"},"PeriodicalIF":9.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026713","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}
引用次数: 0
PAQR5 drives the malignant progression and shapes the immunosuppressive microenvironment of hepatocellular carcinoma by activating the NF-κB signaling. PAQR5通过激活NF-κB信号通路,驱动肝癌恶性进展并形成免疫抑制微环境。
IF 9.5 2区 医学
Biomarker Research Pub Date : 2025-05-07 DOI: 10.1186/s40364-025-00785-z
Ruida Yang, Huanhuan Wang, Cong Wu, Yu Shi, Hanqi Li, Xinyue Bao, Yuqian Yang, Shaoshan Han, Xue Yang, Jie Tao, Hao Sun, Shaobo Wu, Liankang Sun
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