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Reveal the regulatory role of DDX10 in diffuse large B-cell lymphoma: binding with FBL to promote cell proliferation and invasion 揭示DDX10在弥漫性大b细胞淋巴瘤中的调节作用:与FBL结合促进细胞增殖和侵袭
IF 3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-12-01 DOI: 10.1016/j.mcp.2025.102057
Xin Chen, Weiqing Chen

Background

Diffuse large B cell lymphoma (DLBCL) is a heterogeneous malignancy with an unidentified molecular etiology. This study aims to investigate the role of DEAD-box helicase 10 (DDX10), a novel carcinogenic gene, in DLBCL.

Methods

The expression of DDX10 in DLBCL was analyzed by the GEPIA2 bioinformatics tool. DDX10 and fibrillarin (FBL) expressions in DLBCL patients’ cancer tissues and cell lines were measured via quantitative real-time reverse transcription polymerase chain reaction. RNA immunoprecipitation assay was used to confirm FBL-DDX10 interaction. The effects of DDX10/FBL overexpression and knockdown on cell viability, invasion, and Wnt/β-catenin pathway proteins were evaluated in DLBCL cell lines.

Results

DDX10 and FBL exhibited elevated expression levels in patients with DLBCL, particularly in those with stage III or IV DLBCL. DDX10 can bind to FBL in DLBCL cells. Silencing of DDX10 or FBL suppressed viability, proliferation and invasion, and downregulated the expressions of β-catenin, cyclin D1, and c-Myc proteins in DLBCL cells. The regulatory impact of DDX10 or FBL silencing on DLBCL cells was counteracted by the overexpression of FBL or DDX10.

Conclusion

DDX10 contributes to the proliferation and invasion of DLBCL cells via positively regulating FBL, highlighting the DDX10–FBL axis as a potential therapeutic target. This work provides new insights into DLBCL pathogenesis and underscores the biomedical relevance of targeting DDX10–FBL.
背景:弥漫性大B细胞淋巴瘤(DLBCL)是一种分子病因不明的异质性恶性肿瘤。本研究旨在探讨一种新型致癌基因DEAD-box解旋酶10 (DDX10)在DLBCL中的作用。方法采用GEPIA2生物信息学工具分析DDX10在DLBCL中的表达。采用实时定量逆转录聚合酶链反应检测DLBCL患者肿瘤组织和细胞系中DDX10和纤原蛋白(FBL)的表达。RNA免疫沉淀法证实FBL-DDX10相互作用。研究了DDX10/FBL过表达和敲低对DLBCL细胞活力、侵袭性和Wnt/β-catenin通路蛋白的影响。结果ddx10和FBL在DLBCL患者中表达水平升高,特别是在III期或IV期DLBCL患者中。DDX10可与DLBCL细胞中的FBL结合。DDX10或FBL的沉默抑制了DLBCL细胞的活力、增殖和侵袭,下调了β-catenin、cyclin D1和c-Myc蛋白的表达。DDX10或FBL沉默对DLBCL细胞的调控作用被FBL或DDX10的过表达所抵消。结论ddx10通过正调控FBL参与DLBCL细胞的增殖和侵袭,提示DDX10-FBL轴可能是潜在的治疗靶点。这项工作为DLBCL的发病机制提供了新的见解,并强调了靶向DDX10-FBL的生物医学相关性。
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引用次数: 0
Prognostic value of composite inflammatory prognostic model in pancreatic cancer 胰腺癌复合炎性预后模型的预后价值。
IF 3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-11-17 DOI: 10.1016/j.mcp.2025.102056
Qian Wei , Ze Li , Honglei Feng , Jingya Zhang , Lijuan Wei

Introduction

Pancreatic cancer (PC) remains one of the most lethal malignancies worldwide, creating a critical need for reliable prognostic biomarkers, particularly those reflecting tumor microenvironment dynamics.

Methods

We investigated the combined prognostic value of a composite inflammatory prognostic model for PC progression. A retrospective cohort analysis of 171 patients with PC was conducted using receiver operating characteristic (ROC) curve analysis, along with univariate and multivariate Cox regression analyses. Survival curves were plotted using the Kaplan-Meier method. A clinical prognostic nomogram was constructed based on independent prognostic factors.

Results

ROC curve analysis demonstrated that C-reactive protein-to-lymphocyte ratio (CLR) had the highest predictive accuracy for 3-year survival. Survival analysis revealed that TNM stage, CA19-9, CEA, neutrophil count, CRP level, the neutrophil-to-lymphocyte ratio (NLR), and CLR were significantly associated with overall survival. Multivariate Cox regression analysis confirmed that advanced lymphatic metastasis, advanced TNM stage, elevated CA19-9, elevated CEA, elevated neutrophil count, elevated NLR, and elevated CLR were independent prognostic factors. The prognostic nomogram incorporating these variables exhibited robust discriminative capacity and well-calibrated predictions of survival. Using the inflammatory prognostic model, patients in the high-risk group had a significantly shorter median overall survival than those in the low-risk group, with strong predictive accuracy for 1-year and 3-year survival. Validation in a subgroup of patients with pancreatic ductal adenocarcinoma further supported the clinical utility of the model, showing superior 3-year predictive performance and a pronounced survival disparity between the risk groups.

Conclusions

A combination of inflammatory and clinical markers can effectively predict the prognosis of pancreatic cancer. The constructed composite inflammatory prognostic model demonstrated high clinical practical value and provided a reliable tool for individualized prognostic risk assessment.
胰腺癌(PC)仍然是世界上最致命的恶性肿瘤之一,因此迫切需要可靠的预后生物标志物,特别是那些反映肿瘤微环境动态的生物标志物。方法:我们研究了复合炎症预后模型对PC进展的综合预后价值。采用受试者工作特征(ROC)曲线分析,结合单因素和多因素Cox回归分析,对171例PC患者进行回顾性队列分析。采用Kaplan-Meier法绘制生存曲线。基于独立预后因素构建临床预后图。结果:ROC曲线分析显示,c反应蛋白与淋巴细胞比值(CLR)对3年生存率的预测准确性最高。生存分析显示,TNM分期、CA19-9、CEA、中性粒细胞计数、CRP水平、中性粒细胞与淋巴细胞比值(NLR)和CLR与总生存率显著相关。多因素Cox回归分析证实,晚期淋巴转移、晚期TNM分期、CA19-9升高、CEA升高、中性粒细胞计数升高、NLR升高、CLR升高是独立的预后因素。纳入这些变量的预后nomogram显示出强大的判别能力和对生存的精确预测。使用炎症预后模型,高危组患者的中位总生存期明显短于低危组患者,对1年和3年生存期的预测准确性较强。在胰腺导管腺癌患者亚组中的验证进一步支持了该模型的临床实用性,显示出优越的3年预测性能和风险组之间明显的生存差异。结论:炎症指标与临床指标相结合可有效预测胰腺癌预后。所构建的复合炎症预后模型具有较高的临床实用价值,为个体化预后风险评估提供了可靠的工具。
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引用次数: 0
Impact of preoperative clinical patient parameters on surgically obtained brain metastasis samples for translational research 术前临床患者参数对手术获得的脑转移瘤样本的影响
IF 3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-11-04 DOI: 10.1016/j.mcp.2025.102055
Adrian Rombach , Maximilian Geissler , Liu Xiao , Lina-Elisabeth Qasem , Lena Stange , Vincent Prinz , Daniel Jussen , Somaya Landolsi , Konstantinos D. Kokkaliaris , Hind Medyouf , Lisa Sevenich , Pia Zeiner , Yvonne Reiss , Pinar Cakmak , Moritz Armbrust , Katharina J. Weber , Karl Heinz Plate , Stefan Offermanns , Thomas Broggini , Marcus Czabanka
Human tissue samples are a crucial resource for cancer research, offering key insights into physiological and pathological processes while enabling comprehensive characterization of molecular signatures across cancer subtypes. Recent advances in genetic analysis techniques lead to a substantiall expansion of specific molecular pathways knowledge. The application of these technologies to fresh tissue samples from patients undergoing surgical resection for metastatic disease represents a promising approach to gain a deeper understanding of the biology of brain metastasis. Brain metastases remain particularly challenging due to their poor prognosis and the complex mechanisms underlying central nervous system invasion. This study sought to identify preoperative factors influencing the research utility of fresh brain metastasis tissue samples. A pipeline was established to transfer fresh, surplus tissue from surgical resections to research laboratories with histological quality assessment. Of the fifty-five fresh specimens collected, thirty-eight (69 %) were classified as suitable for further research applications. Statistical analysis revealed that only two factors significantly affected sample quality. First, the extent of MRI-derived necrosis was significantly higher in unsuitable samples (mean 18.0 %) than in suitable samples (mean 8.3 %) (p = 0.0273). Second, prior treatment with target-specific therapeutics (TST) was associated with a lower proportion of suitable samples (47 %) compared to no prior TST (79 %) (p = 0.018). Logistic regression confirmed these variables as significant predictors, with MRI-derived necrosis (odds ratio 1.049) and target-specific therapy exposure (odds ratio 4.486) independently increasing the likelihood of obtaining suboptimal samples. Other parameters, including age, gender, metastasis volume, localization, primary cancer site, and other therapeutic interventions, showed no significant impact on sample quality. Based on these findings, the collection pipeline was modified to include evaluation by board-certified neuropathologists before samples are used for research purposes, improving the efficiency of translational research utilizing brain metastasis tissue.
人体组织样本是癌症研究的重要资源,提供了对生理和病理过程的关键见解,同时能够全面表征癌症亚型的分子特征。遗传分析技术的最新进展导致了特定分子途径知识的实质性扩展。将这些技术应用于转移性疾病手术切除患者的新鲜组织样本,代表了一种有希望的方法,可以更深入地了解脑转移的生物学。由于预后不良和中枢神经系统侵袭的复杂机制,脑转移瘤仍然特别具有挑战性。本研究旨在确定影响新鲜脑转移组织样本研究效用的术前因素。建立了一条管道,将手术切除的新鲜剩余组织转移到研究实验室进行组织学质量评估。在收集到的55个新鲜标本中,有38个(69%)被归类为适合进一步研究应用。统计分析显示,只有两个因素显著影响样品质量。首先,mri来源的坏死程度在不合适的样本中(平均18.0%)明显高于合适的样本(平均8.3%)(p=0.0273)。其次,与没有接受过靶向特异性治疗(TST)的患者相比,接受过靶向特异性治疗(TST)的患者获得合适样本的比例较低(47%)(p = 0.018)。Logistic回归证实了这些变量是重要的预测因子,mri衍生坏死(比值比1.049)和靶向治疗暴露(比值比4.486)分别增加了获得次优样本的可能性。其他参数,包括年龄、性别、转移量、定位、原发癌部位和其他治疗干预措施,对样本质量没有显著影响。基于这些发现,在样本用于研究目的之前,收集管道进行了修改,包括由委员会认证的神经病理学家进行评估,提高了利用脑转移组织进行转化研究的效率。
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引用次数: 0
Identification of lymphangiogenesis-related diagnostic model for predicting abdominal aortic aneurysm onset and progression and validation of lymphopoiesis in abdominal aortic aneurysm 预测腹主动脉瘤发生发展的淋巴管生成相关诊断模型的建立及腹主动脉瘤淋巴生成的验证。
IF 3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-11-01 DOI: 10.1016/j.mcp.2025.102054
Su Qin , Jing Zhang , Meifang Cao , Tao Jiang , Baohong Jiang
This study aims to explore the lymphangiogenesis (LG)-related diagnostic markers of abdominal aortic aneurysm (AAA) through bioinformatics, as well as the alteration of the regional lymphatic system during the progression of AAA and the influence of lymphatic drainage obstruction on AAA progression. 2957 differentially expressed genes (DEGs) were identified between the AAA patient group and the healthy donor group in Gene Expression Omnibus microarray datasets. Subsequently, the DEGs and the LG gene were intersected, and 93 genes were obtained. Weighted gene co-expression network analysis (WGCNA) was performed to obtain module genes. Module genes intersected with the above 93 genes, and 26 genes were obtained. Five hub genes (HSPA5, RAB10, RAB1A, RAF1, SMAD4) identified by machine learning may serve as diagnostic candidates for AAA patients through nomogram and ROC evaluation. Gene set enrichment analysis (GSEA) and immune infiltration analysis were performed further to understand the function of these candidate genes and explore the effect of immunity in AAA, respectively. By establishing an AAA animal model, it was found that the iliac lymph nodes around the abdominal aorta were significantly enlarged, and the number and lumen size of lymphatic vessels in the vessel wall were both significantly increased during the progression of AAA. Additionally, AAA was significantly promoted by ligating lymphatic vessels, which caused lymphatic drainage obstruction around the abdominal aorta. Our findings have the potential to enhance knowledge about the development and diagnosis of AAA.
本研究旨在通过生物信息学的方法探讨腹主动脉瘤(AAA)的淋巴管生成(LG)相关诊断指标,以及AAA进展过程中局部淋巴系统的改变及淋巴引流阻塞对AAA进展的影响。在基因表达集成芯片(Gene Expression Omnibus microarray)数据集中,鉴定出AAA患者组与健康供者组之间存在2957个差异表达基因。随后,将DEGs与LG基因进行交叉,得到93个基因。采用加权基因共表达网络分析(WGCNA)获得模块基因。模块基因与上述93个基因相交,得到26个基因。通过机器学习识别的5个中心基因(HSPA5、RAB10、RAB1A、RAF1、SMAD4)可通过nomogram和ROC评价作为AAA患者的候选诊断基因。进一步进行基因集富集分析(GSEA)和免疫浸润分析,分别了解这些候选基因的功能,探讨免疫在AAA中的作用。通过建立AAA动物模型发现,在AAA的进展过程中,腹主动脉周围的髂淋巴结明显增大,血管壁淋巴管数量和管腔大小均明显增加,结扎淋巴管可明显促进AAA,造成腹主动脉周围淋巴管引流阻塞。我们的发现有可能提高对AAA的发展和诊断的认识。
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引用次数: 0
Exploiting network-based drug repositioning to target metastasis in colorectal cancer: In-Silico prediction and in-vitro evidence 利用基于网络的药物重新定位靶向结直肠癌转移:计算机预测和体外证据。
IF 3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-10-01 DOI: 10.1016/j.mcp.2025.102053
Mohammad Javad Bazyari , Ali Ahmadizad Firouzjaei , Seyed Mahdi Ahmadi , Mohsen Khorashadizadeh , Seyed Hamid Aghaee-Bakhtiari
Metastasis is a major challenge in colorectal cancer (CRC) treatment. The incidence of regional and distant stages has increased during the past decade and the 5-year survival of metastatic CRC patients is 20 %. Although there is a necessity to develop systematic treatment, the cost and time of novel drug discovery hinder this progress. Drug repositioning simplifies this process by accelerating regulatory processes in drug discovery. Here we used a systems biology approach to find key player genes in the metastasis. First, we found differentially expressed genes in metastatic tissue compared to primary tumors. Then, we constructed and analyzed the protein-protein interaction (PPI) network to find hub genes and subjected them to query in the DrugBank database. We found plasminogen (PLG) is the hub gene in the constructed PPI network and tranexamic acid (TXA) is its known inhibitor with clinically approved antifibrinolytic activity. Pathway enrichment analysis showed that PLG is involved in matrix remodeling, Platelet activation, and cell energy production through insulin-growth factor uptake in colorectal cancer cells which are important processes during metastasis. We further explored the CPTAC-COAD proteomics data and found that the PLG level is significantly higher in stage IV compared to stage I. Interestingly, we found that PLG is correlated with mutation rate. We then investigated the effect of TXA on SW480 cells' mobility and migration by scratch assay and transwell migration assay. Both assays indicated that TXA can significantly inhibit the cells’ migratory potential.
转移是结直肠癌(CRC)治疗的主要挑战。在过去十年中,局部和远处分期的发生率有所增加,转移性CRC患者的5年生存率为20%。虽然有必要开发系统的治疗方法,但新药发现的成本和时间阻碍了这一进展。药物重新定位通过加速药物发现的监管过程简化了这一过程。在这里,我们使用系统生物学方法来寻找转移的关键基因。首先,我们在转移组织中发现了与原发肿瘤相比的差异表达基因。然后,我们构建并分析了蛋白质-蛋白质相互作用(PPI)网络来寻找枢纽基因,并将其在DrugBank数据库中进行查询。我们发现纤溶酶原(PLG)是构建的PPI网络中的枢纽基因,氨甲环酸(TXA)是其已知的抑制剂,具有临床批准的抗纤溶活性。途径富集分析表明,PLG参与结肠直肠癌细胞基质重塑、血小板活化和通过胰岛素生长因子摄取产生细胞能量,这些都是转移过程中的重要过程。我们进一步研究了CPTAC-COAD蛋白质组学数据,发现PLG水平在IV期明显高于i期。有趣的是,我们发现PLG与突变率相关。然后,我们通过划痕实验和transwell迁移实验研究了TXA对SW480细胞迁移和迁移的影响。两项实验均表明,TXA能显著抑制细胞的迁移潜能。
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引用次数: 0
CRISPR/Cas as a tool to overcome drug resistance in cancer: From challenge to opportunity CRISPR/Cas作为战胜癌症耐药的工具:从挑战到机遇。
IF 3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-09-26 DOI: 10.1016/j.mcp.2025.102052
Bashdar Mahmud Hussen , Snur Rasool Abdullah , Hazha Jamal Hidayat , Mark C. Glassy , Arash Safarzadeh , Alireza Komaki , Majid Samsami , Mohammad Taheri
Drug resistance remains a significant challenge in cancer therapy, often resulting in treatment failure, tumor progression, and metastasis. The underlying resistance mechanisms—including genetic mutations, epigenetic alterations, and modifications in drug efflux pathways—are complex and not yet fully understood. This review explores the application of CRISPR-Cas gene editing technology in understanding and overcoming drug resistance in cancer. It focuses on how CRISPR can identify and target resistance-associated genes to restore drug sensitivity. CRISPR-based approaches enable precise genetic modifications that offer new insights into the molecular basis of drug resistance. The technology has shown promise in dissecting resistance mechanisms and developing targeted therapeutic strategies. Nevertheless, key limitations such as inefficient delivery systems, off-target effects, and limited specificity hinder clinical translation. Current efforts focus on improving guide RNA design, creating more effective delivery vectors, and integrating CRISPR with existing treatments. CRISPR-Cas technology holds significant potential to address drug resistance in cancer by enabling targeted genetic interventions. Continued advancements are required to enhance its safety, specificity, and delivery, paving the way for its integration into future clinical applications.
耐药仍然是癌症治疗中的一个重大挑战,经常导致治疗失败、肿瘤进展和转移。潜在的耐药机制——包括基因突变、表观遗传改变和药物外排途径的改变——是复杂的,尚未完全了解。本文综述了CRISPR-Cas基因编辑技术在了解和克服癌症耐药中的应用。它的重点是CRISPR如何识别和靶向耐药性相关基因以恢复药物敏感性。基于crispr的方法实现了精确的基因修饰,为耐药性的分子基础提供了新的见解。该技术在解剖耐药机制和开发靶向治疗策略方面显示出前景。然而,关键的限制,如低效率的输送系统,脱靶效应和有限的特异性阻碍了临床翻译。目前的工作重点是改进引导RNA设计,创造更有效的传递载体,以及将CRISPR与现有治疗方法结合起来。CRISPR-Cas技术通过实现靶向基因干预,具有解决癌症耐药问题的巨大潜力。需要持续的进步来增强其安全性、特异性和递送,为其整合到未来的临床应用铺平道路。
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引用次数: 0
Exosome biosensors for detection of ovarian cancer 检测卵巢癌的外泌体生物传感器。
IF 3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-09-19 DOI: 10.1016/j.mcp.2025.102051
Asma Vafadar , Negar Nayerain Jazi , Melika Eghtesadi , Sajad Ehtiati , Ahmad Movahedpour , Amir Savardashtaki
Ovarian cancer (OC) is one of the most aggressive gynecologic malignancies, largely due to its asymptomatic progression and frequent diagnosis at an advanced stage. Early detection is essential for improving patient survival rates. Exosomes, small extracellular vesicles secreted by cells, are actively involved in OC progression and have been recognized as potential biomarkers for early diagnosis. Over the past decade, advancements in exosome research have emphasized the need for detection methods that are not only sensitive and reliable but also practical for clinical use. However, conventional approaches often face challenges such as limited sensitivity and complex sample preparation. Biosensors have emerged as a promising alternative, offering benefits such as non-invasiveness and improved analytical performance. This review examines recent developments in electrochemical, optical, and electrical biosensors for detecting OC-related exosomes, discussing their sensitivity, specificity, and potential applications in clinical settings.
卵巢癌(OC)是最具侵袭性的妇科恶性肿瘤之一,主要是由于其无症状进展和经常在晚期诊断。早期发现对提高患者存活率至关重要。外泌体是细胞分泌的小细胞外囊泡,积极参与肿瘤的进展,被认为是早期诊断的潜在生物标志物。在过去的十年中,外泌体研究的进展强调了对检测方法的需求,这种检测方法不仅敏感可靠,而且对临床应用也很实用。然而,传统方法经常面临诸如灵敏度有限和样品制备复杂等挑战。生物传感器已经成为一种很有前途的替代方案,它提供了诸如非侵入性和改进的分析性能等好处。本文综述了用于检测oc相关外泌体的电化学、光学和电学生物传感器的最新进展,讨论了它们的敏感性、特异性和在临床环境中的潜在应用。
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引用次数: 0
Corrigendum to "Establishment of CRISPR/Cas9 lineage tracking technology for pig embryos" [Molecular and Cellular Probes 83 (2025) 102046]. “猪胚胎CRISPR/Cas9谱系追踪技术的建立”[Molecular and Cellular Probes 83(2025) 102046]的勘误表。
IF 3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-09-13 DOI: 10.1016/j.mcp.2025.102050
Xiang-Qian Meng, Xue-Ling Xu, Yu Gao, Shou-Long Deng
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引用次数: 0
Spatial and functional characterization of IL1RL1+ mast cells reveals immune regulatory roles in renal cancer IL1RL1+肥大细胞的空间和功能特征揭示了肾癌的免疫调节作用
IF 3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-09-03 DOI: 10.1016/j.mcp.2025.102049
Zeyu Li , Chunfeng Zhang , Kuo Ma , Guangye Han , Weihang Song , Minghao Yue , Shuaiqi Chen

Background

Interleukin-1 receptor-like 1 (IL1RL1, also known as ST2) plays a critical role in immune regulation. Pan-cancer analysis has revealed that IL1RL1 is closely associated with cellular immune functions; however, its role in clear cell renal cell carcinoma (ccRCC) and the tumor microenvironment (TME) remains poorly defined.

Methods

We analyzed IL1RL1 expression patterns using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) were employed to investigate the cellular localization and biological functions of IL1RL1 in ccRCC. In addition, IL1RL1 knockout experiments were conducted to explore its potential role in antigen presentation.

Results

Compared to adjacent normal tissues, IL1RL1 expression was significantly downregulated in renal cancer tissues. Higher IL1RL1 expression correlated with improved patient prognosis, suggesting its potential as an independent prognostic biomarker. IL1RL1 was predominantly expressed in mast cells, with higher levels observed in adjacent normal tissues than in tumor tissues, implying a regulatory role in tumor immunity. Subset analysis revealed that IL1RL1-high mast cells were enriched in immune-inflammatory functions, including leukocyte activation, chemokine production, and antigen presentation. Cell–cell communication analysis further demonstrated that IL1RL1+ mast cells may enhance CD8+ cytotoxic T cell activation via the MHC-I signaling pathway. Spatial transcriptomics and multiplex immunohistochemistry (mIHC) confirmed the spatial co-localization of IL1RL1+ mast cells and T cells within the TME. Furthermore, IL1RL1 knockout led to a reduction in HLA-A expression, providing functional evidence for its involvement in antigen presentation.

Conclusion

Our findings highlight the immune-regulatory role of IL1RL1+ mast cells in ccRCC. IL1RL1 may contribute to anti-tumor immunity through the modulation of antigen presentation and CD8+ T cell activation, offering new insights into its potential as a prognostic biomarker and therapeutic target in renal cancer.
背景:白细胞介素-1受体样1 (Interleukin-1 receptor-like 1, IL1RL1,又称ST2)在免疫调节中起关键作用。泛癌分析显示,IL1RL1与细胞免疫功能密切相关;然而,其在透明细胞肾细胞癌(ccRCC)和肿瘤微环境(TME)中的作用仍不清楚。方法:利用癌症基因组图谱(TCGA)和基因表达图谱(GEO)数据库的数据分析IL1RL1的表达模式。利用单细胞RNA测序(scRNA-seq)和空间转录组学(ST)研究IL1RL1在ccRCC中的细胞定位和生物学功能。此外,我们还进行了IL1RL1敲除实验,以探索其在抗原呈递中的潜在作用。结果:与邻近正常组织相比,肾癌组织中IL1RL1表达明显下调。较高的IL1RL1表达与患者预后改善相关,提示其作为独立预后生物标志物的潜力。IL1RL1主要在肥大细胞中表达,其在邻近正常组织中的表达水平高于在肿瘤组织中的表达水平,表明其在肿瘤免疫中具有调节作用。亚群分析显示,il1rl1高的肥大细胞具有丰富的免疫炎症功能,包括白细胞活化、趋化因子产生和抗原呈递。细胞间通讯分析进一步表明,IL1RL1+肥大细胞可能通过MHC-I信号通路增强CD8+细胞毒性T细胞的活化。空间转录组学和多重免疫组织化学(mIHC)证实了IL1RL1+肥大细胞和T细胞在TME内的空间共定位。此外,IL1RL1敲除导致HLA-A表达减少,为其参与抗原递呈提供了功能证据。结论:我们的研究结果强调了IL1RL1+肥大细胞在ccRCC中的免疫调节作用。IL1RL1可能通过调节抗原呈递和CD8+ T细胞活化来促进抗肿瘤免疫,这为其作为肾癌预后生物标志物和治疗靶点的潜力提供了新的见解。
{"title":"Spatial and functional characterization of IL1RL1+ mast cells reveals immune regulatory roles in renal cancer","authors":"Zeyu Li ,&nbsp;Chunfeng Zhang ,&nbsp;Kuo Ma ,&nbsp;Guangye Han ,&nbsp;Weihang Song ,&nbsp;Minghao Yue ,&nbsp;Shuaiqi Chen","doi":"10.1016/j.mcp.2025.102049","DOIUrl":"10.1016/j.mcp.2025.102049","url":null,"abstract":"<div><h3>Background</h3><div>Interleukin-1 receptor-like 1 (IL1RL1, also known as ST2) plays a critical role in immune regulation. Pan-cancer analysis has revealed that IL1RL1 is closely associated with cellular immune functions; however, its role in clear cell renal cell carcinoma (ccRCC) and the tumor microenvironment (TME) remains poorly defined.</div></div><div><h3>Methods</h3><div>We analyzed IL1RL1 expression patterns using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) were employed to investigate the cellular localization and biological functions of IL1RL1 in ccRCC. In addition, IL1RL1 knockout experiments were conducted to explore its potential role in antigen presentation.</div></div><div><h3>Results</h3><div>Compared to adjacent normal tissues, IL1RL1 expression was significantly downregulated in renal cancer tissues. Higher IL1RL1 expression correlated with improved patient prognosis, suggesting its potential as an independent prognostic biomarker. IL1RL1 was predominantly expressed in mast cells, with higher levels observed in adjacent normal tissues than in tumor tissues, implying a regulatory role in tumor immunity. Subset analysis revealed that IL1RL1-high mast cells were enriched in immune-inflammatory functions, including leukocyte activation, chemokine production, and antigen presentation. Cell–cell communication analysis further demonstrated that IL1RL1<sup>+</sup> mast cells may enhance CD8<sup>+</sup> cytotoxic T cell activation via the MHC-I signaling pathway. Spatial transcriptomics and multiplex immunohistochemistry (mIHC) confirmed the spatial co-localization of IL1RL1<sup>+</sup> mast cells and T cells within the TME. Furthermore, IL1RL1 knockout led to a reduction in HLA-A expression, providing functional evidence for its involvement in antigen presentation.</div></div><div><h3>Conclusion</h3><div>Our findings highlight the immune-regulatory role of IL1RL1<sup>+</sup> mast cells in ccRCC. IL1RL1 may contribute to anti-tumor immunity through the modulation of antigen presentation and CD8<sup>+</sup> T cell activation, offering new insights into its potential as a prognostic biomarker and therapeutic target in renal cancer.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"84 ","pages":"Article 102049"},"PeriodicalIF":3.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Non-coding RNAs in chronic lymphocytic leukemia: A systematic review and meta-analysis to decode the diagnostic potential 慢性淋巴细胞白血病中的非编码rna:一项系统综述和解码诊断潜力的荟萃分析。
IF 3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-08-30 DOI: 10.1016/j.mcp.2025.102048
Amir Hossein Aghayan , Ali Arab , Shadi Haddadi , Amir Atashi

Background

Chronic lymphocytic leukemia (CLL) comprises around 25–30 % of leukemia cases in the West. Emerging evidence underscores the role of non-coding RNAs (ncRNAs) like miRNAs, lncRNAs, and CircRNAs in CLL pathogenesis and regulation. The unique properties of ncRNAs have given the potential as non-invasive diagnostic biomarkers for CLL.

Methods

PubMed, Web of Science, Scopus, ProQuest, and Embase databases were searched (from inception up to January 2024) for studies addressing the correlation of ncRNA expression levels with diagnosis of CLL. The QUADAS-2 tool was employed to evaluate the risk of bias in the included studies. The GRADE approach evaluated the certainty of the evidence for diagnostic test accuracy.

Results

A total of 14 studies including 934 CLL patients were analyzed. Evaluations focused on miRNAs and CircRNAs due to sufficient primary data. For miRNAs, pooled sensitivity: 0.84, specificity: 0.98, positive likelihood ratio (PLR): 42.19, negative likelihood ratio (NLR): 0.16, diagnostic odds ratio (DOR): 260.14; area under the curve (AUC): 0.96. For CircRNAs, pooled sensitivity: 0.69, specificity: 0.77, PLR: 3.01, NLR: 0.40, DOR: 7.51, AUC: 0.80. GRADE assessments indicated very low certainty of evidence for miRNAs and low certainty for CircRNAs.

Conclusion

Both miRNAs and CircRNAs appear to hold promise as non-invasive diagnostic biomarkers in CLL, with miRNAs demonstrating higher diagnostic performance. However, based on the GRADE assessments, the certainty of evidence may undermine the reliability of the pooled estimates. Future studies with rigorous design, larger sample sizes, and standardized protocols are essential to strengthen the certainty of evidence.
背景:慢性淋巴细胞白血病(CLL)约占西方白血病病例的25-30%。新出现的证据强调了非编码rna (ncRNAs)如miRNAs、lncRNAs和CircRNAs在CLL发病机制和调控中的作用。ncrna的独特特性赋予了其作为CLL非侵入性诊断生物标志物的潜力。方法:检索PubMed, Web of Science, Scopus, ProQuest和Embase数据库(从成立到2024年1月),寻找ncRNA表达水平与CLL诊断相关性的研究。采用QUADAS-2工具评估纳入研究的偏倚风险。GRADE方法评估诊断测试准确性证据的确定性。结果:共纳入14项研究,共纳入934例CLL患者。由于有足够的原始数据,评估主要集中在mirna和circrna上。对于miRNAs,合并敏感性:0.84,特异性:0.98,阳性似然比(PLR): 42.19,阴性似然比(NLR): 0.16,诊断优势比(DOR): 260.14;曲线下面积(AUC): 0.96。对于CircRNAs,总敏感性为0.69,特异性为0.77,PLR为3.01,NLR为0.40,DOR为7.51,AUC为0.80。GRADE评估表明,mirna和circrna的证据确定性非常低。结论:mirna和circrna似乎都有望成为CLL的非侵入性诊断生物标志物,其中mirna表现出更高的诊断性能。然而,基于GRADE评估,证据的确定性可能会破坏汇总估计的可靠性。严格设计、更大样本量和标准化方案的未来研究对于加强证据的确定性至关重要。
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Molecular and Cellular Probes
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