Biomarker Research最新文献

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Roles of posttranslational modifications in lipid metabolism and cancer progression. 翻译后修饰在脂质代谢和癌症进展中的作用。
IF 9.5 2区 医学
Biomarker Research Pub Date : 2024-11-18 DOI: 10.1186/s40364-024-00681-y
Tianyu Feng, He Zhang, Yanjie Zhou, Yalan Zhu, Shiya Shi, Kai Li, Ping Lin, Jie Chen
{"title":"Roles of posttranslational modifications in lipid metabolism and cancer progression.","authors":"Tianyu Feng, He Zhang, Yanjie Zhou, Yalan Zhu, Shiya Shi, Kai Li, Ping Lin, Jie Chen","doi":"10.1186/s40364-024-00681-y","DOIUrl":"10.1186/s40364-024-00681-y","url":null,"abstract":"<p><p>Lipid metabolism reprogramming has emerged as a hallmark of malignant tumors. Lipids represent a complex group of biomolecules that not only compose the essential components of biological membranes and act as an energy source, but also function as messengers to integrate various signaling pathways. In tumor cells, de novo lipogenesis plays a crucial role in acquiring lipids to meet the demands of rapid growth. Increasing evidence has suggested that dysregulated lipid metabolism serves as a driver of cancer progression. Posttranslational modifications (PTMs), which occurs in most eukaryotic proteins throughout their lifetimes, affect the activity, abundance, function, localization, and interactions of target proteins. PTMs of crucial molecules are potential intervention sites and are emerging as promising strategies for the cancer treatment. However, there is limited information available regarding the PTMs that occur in cancer lipid metabolism and the potential treatment strategies associated with these PTMs. Herein, we summarize current knowledge of the roles and regulatory mechanisms of PTMs in lipid metabolism. Understanding the roles of PTMs in lipid metabolism in cancer could provide valuable insights into tumorigenesis and progression. Moreover, targeting PTMs in cancer lipid metabolism might represent a promising novel therapeutic strategy.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"141"},"PeriodicalIF":9.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11571667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649683","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
Advanced single-cell and spatial analysis with high-multiplex characterization of circulating tumor cells and tumor tissue in prostate cancer: Unveiling resistance mechanisms with the CoDuCo in situ assay. 对前列腺癌循环肿瘤细胞和肿瘤组织进行先进的单细胞和空间分析及高倍表征:利用 CoDuCo 原位测定揭示抗药性机制。
IF 9.5 2区 医学
Biomarker Research Pub Date : 2024-11-16 DOI: 10.1186/s40364-024-00680-z
Lilli Bonstingl, Margret Zinnegger, Katja Sallinger, Karin Pankratz, Christin-Therese Müller, Elisabeth Pritz, Corinna Odar, Christina Skofler, Christine Ulz, Lisa Oberauner-Wappis, Anatol Borrás-Cherrier, Višnja Somođi, Ellen Heitzer, Thomas Kroneis, Thomas Bauernhofer, Amin El-Heliebi
{"title":"Advanced single-cell and spatial analysis with high-multiplex characterization of circulating tumor cells and tumor tissue in prostate cancer: Unveiling resistance mechanisms with the CoDuCo in situ assay.","authors":"Lilli Bonstingl, Margret Zinnegger, Katja Sallinger, Karin Pankratz, Christin-Therese Müller, Elisabeth Pritz, Corinna Odar, Christina Skofler, Christine Ulz, Lisa Oberauner-Wappis, Anatol Borrás-Cherrier, Višnja Somođi, Ellen Heitzer, Thomas Kroneis, Thomas Bauernhofer, Amin El-Heliebi","doi":"10.1186/s40364-024-00680-z","DOIUrl":"10.1186/s40364-024-00680-z","url":null,"abstract":"<p><strong>Background: </strong>Metastatic prostate cancer is a highly heterogeneous and dynamic disease and practicable tools for patient stratification and resistance monitoring are urgently needed. Liquid biopsy analysis of circulating tumor cells (CTCs) and circulating tumor DNA are promising, however, comprehensive testing is essential due to diverse mechanisms of resistance. Previously, we demonstrated the utility of mRNA-based in situ padlock probe hybridization for characterizing CTCs.</p><p><strong>Methods: </strong>We have developed a novel combinatorial dual-color (CoDuCo) assay for in situ mRNA detection, with enhanced multiplexing capacity, enabling the simultaneous analysis of up to 15 distinct markers. This approach was applied to CTCs, corresponding tumor tissue, cancer cell lines, and peripheral blood mononuclear cells for single-cell and spatial gene expression analysis. Using supervised machine learning, we trained a random forest classifier to identify CTCs. Image analysis and visualization of results was performed using open-source Python libraries, CellProfiler, and TissUUmaps.</p><p><strong>Results: </strong>Our study presents data from multiple prostate cancer patients, demonstrating the CoDuCo assay's ability to visualize diverse resistance mechanisms, such as neuroendocrine differentiation markers (SYP, CHGA, NCAM1) and AR-V7 expression. In addition, druggable targets and predictive markers (PSMA, DLL3, SLFN11) were detected in CTCs and formalin-fixed, paraffin-embedded tissue. The machine learning-based CTC classification achieved high performance, with a recall of 0.76 and a specificity of 0.99.</p><p><strong>Conclusions: </strong>The combination of high multiplex capacity and microscopy-based single-cell analysis is a unique and powerful feature of the CoDuCo in situ assay. This synergy enables the simultaneous identification and characterization of CTCs with epithelial, epithelial-mesenchymal, and neuroendocrine phenotypes, the detection of CTC clusters, the visualization of CTC heterogeneity, as well as the spatial investigation of tumor tissue. This assay holds significant potential as a tool for monitoring dynamic molecular changes associated with drug response and resistance in prostate cancer.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"140"},"PeriodicalIF":9.5,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644586","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
Pathophysiology and preclinical relevance of experimental graft-versus-host disease in humanized mice. 人源化小鼠实验性移植物抗宿主病的病理生理学和临床前相关性。
IF 9.5 2区 医学
Biomarker Research Pub Date : 2024-11-14 DOI: 10.1186/s40364-024-00684-9
Grégory Ehx, Caroline Ritacco, Frédéric Baron
{"title":"Pathophysiology and preclinical relevance of experimental graft-versus-host disease in humanized mice.","authors":"Grégory Ehx, Caroline Ritacco, Frédéric Baron","doi":"10.1186/s40364-024-00684-9","DOIUrl":"10.1186/s40364-024-00684-9","url":null,"abstract":"<p><p>Graft-versus-host disease (GVHD) is a life-threatening complication of allogeneic hematopoietic cell transplantations (allo-HCT) used for the treatment of hematological malignancies and other blood-related disorders. Until recently, the discovery of actionable molecular targets to treat GVHD and their preclinical testing was almost exclusively based on modeling allo-HCT in mice by transplanting bone marrow and splenocytes from donor mice into MHC-mismatched recipient animals. However, due to fundamental differences between human and mouse immunology, the translation of these molecular targets into the clinic can be limited. Therefore, humanized mouse models of GVHD were developed to circumvent this limitation. In these models, following the transplantation of human peripheral blood mononuclear cells (PBMCs) into immunodeficient mice, T cells recognize and attack mouse organs, inducing GVHD. Thereby, humanized mice provide a platform for the evaluation of the effects of candidate therapies on GVHD mediated by human immune cells in vivo. Understanding the pathophysiology of this xenogeneic GVHD is therefore crucial for the design and interpretation of experiments performed with this model. In this article, we comprehensively review the cellular and molecular mechanisms governing GVHD in the most commonly used model of xenogeneic GVHD: PBMC-engrafted NOD/LtSz-Prkdc<sup>scid</sup>IL2rγ<sup>tm1Wjl</sup> (NSG) mice. By re-analyzing public sequencing data, we also show that the clonal expansion and the transcriptional program of T cells in humanized mice closely reflect those in humans. Finally, we highlight the strengths and limitations of this model, as well as arguments in favor of its biological relevance for studying T-cell reactions against healthy tissues or cancer cells.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"139"},"PeriodicalIF":9.5,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632426","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
Exosomal PSM-E inhibits macrophage M2 polarization to suppress prostate cancer metastasis through the RACK1 signaling axis. 外泌体 PSM-E 通过 RACK1 信号轴抑制巨噬细胞 M2 极化,从而抑制前列腺癌转移。
IF 9.5 2区 医学
Biomarker Research Pub Date : 2024-11-14 DOI: 10.1186/s40364-024-00685-8
Xingliang Qin, Ruoxi Niu, Yongyao Tan, Yuxin Huang, Weishu Ren, Weiwei Zhou, Huiquan Wu, Junlong Zhang, Mingze Xu, Xiang Zhou, Hongyu Guan, Xun Zhu, Yu Chen, Kaiyuan Cao
{"title":"Exosomal PSM-E inhibits macrophage M2 polarization to suppress prostate cancer metastasis through the RACK1 signaling axis.","authors":"Xingliang Qin, Ruoxi Niu, Yongyao Tan, Yuxin Huang, Weishu Ren, Weiwei Zhou, Huiquan Wu, Junlong Zhang, Mingze Xu, Xiang Zhou, Hongyu Guan, Xun Zhu, Yu Chen, Kaiyuan Cao","doi":"10.1186/s40364-024-00685-8","DOIUrl":"10.1186/s40364-024-00685-8","url":null,"abstract":"<p><strong>Background: </strong>It is well-established that understanding the mechanism of prostate cancer (PCa)-associated metastasis is paramount for improving its prognosis. Metastasis is known to involve the communication between tumor-associated macrophages (TAMs) and tumor cells. Exosomes are crucial in mediating this intercellular communication within the tumor microenvironment. Nonetheless, the role of exosomal proteins in PCa metastasis is not yet fully understood. Here, we investigated the mechanisms of prostate cancer-derived exosomal PSM-E on regulating macrophage M2 polarization to suppress tumor invasion and metastasis.</p><p><strong>Methods: </strong>PSM-E levels in exosomes were detected by transmission electron microscopy and Western blotting analysis. The diagnostic value of urine-derived exosomal PSM-E in PCa were evaluated by LC-MS/MS, correlation analysis, and ROC curves analysis. The mechanisms underlying the inhibitory effect of exosomal PSM-E on the M2 polarization of macrophages was investigated by co-IP, IHC staining, and PCa tumorigenesis model, etc. RESULTS: We revealed that exosomal PSM-E is upregulated in exosomes derived from the serum and urine of PCa patients. Clinically, an elevated exosomal PSM-E expression in urine is significantly correlated with an advanced pathological tumor stage and a high Gleason score. Our research also revealed that exosomal PSM-E inhibits prostate cancer cell proliferation, invasion, and metastasis by suppressing macrophage polarization in vitro and in vivo. Furthermore, we provided compelling evidence that exosomal PSM-E inhibits M2 polarization of macrophages by recruiting RACK1 and suppressing the FAK and ERK signaling pathways, consequently suppressing PCa invasion and metastasis. Furthermore, we found that the protease-associated domain of PSM-E and the fourth tryptophan-aspartate repeat of RACK1 are crucial for the interaction between PSM-E and RACK1.</p><p><strong>Conclusions: </strong>Notably, exosomes carrying PSM-E from PCa urine could potentially serve as a biomarker for PCa, and targeting exosomal PSM-E may represent a strategy for preventing tumor progression in this patient population.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"138"},"PeriodicalIF":9.5,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632423","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
From regulation to deregulation of p53 in hematologic malignancies: implications for diagnosis, prognosis and therapy. 血液恶性肿瘤中 p53 从调控到失调:对诊断、预后和治疗的影响。
IF 9.5 2区 医学
Biomarker Research Pub Date : 2024-11-14 DOI: 10.1186/s40364-024-00676-9
Seyed Esmaeil Ahmadi, Elahe Rahimian, Samira Rahimi, Bahman Zarandi, Mehran Bahraini, Maral Soleymani, Seyed Mehrab Safdari, Ashkan Shabannezhad, Niloofar Jaafari, Majid Safa
{"title":"From regulation to deregulation of p53 in hematologic malignancies: implications for diagnosis, prognosis and therapy.","authors":"Seyed Esmaeil Ahmadi, Elahe Rahimian, Samira Rahimi, Bahman Zarandi, Mehran Bahraini, Maral Soleymani, Seyed Mehrab Safdari, Ashkan Shabannezhad, Niloofar Jaafari, Majid Safa","doi":"10.1186/s40364-024-00676-9","DOIUrl":"10.1186/s40364-024-00676-9","url":null,"abstract":"<p><p>The p53 protein, encoded by the TP53 gene, serves as a critical tumor suppressor, playing a vital role in maintaining genomic stability and regulating cellular responses to stress. Dysregulation of p53 is frequently observed in hematological malignancies, significantly impacting disease progression and patient outcomes. This review aims to examine the regulatory mechanisms of p53, the implications of TP53 mutations in various hematological cancers, and emerging therapeutic strategies targeting p53. We conducted a comprehensive literature review to synthesize recent findings related to p53's multifaceted role in hematologic cancers, focusing on its regulatory pathways and therapeutic potential. TP53 mutations in hematological malignancies often lead to treatment resistance and poor prognosis. Current therapeutic strategies, including p53 reactivation and gene therapy, show promise in improving treatment outcomes. Understanding the intricacies of p53 regulation and the consequences of its mutations is essential for developing effective diagnostic and therapeutic strategies in hematological malignancies, ultimately enhancing patient care and survival.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"137"},"PeriodicalIF":9.5,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11565275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632424","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
New strategies for lung cancer diagnosis and treatment: applications and advances in nanotechnology. 肺癌诊断和治疗的新策略:纳米技术的应用和进展。
IF 9.5 2区 医学
Biomarker Research Pub Date : 2024-11-13 DOI: 10.1186/s40364-024-00686-7
Jiaqi Feng, Pengpeng Zhang, Dingli Wang, Yuting Li, Jiaxiong Tan
{"title":"New strategies for lung cancer diagnosis and treatment: applications and advances in nanotechnology.","authors":"Jiaqi Feng, Pengpeng Zhang, Dingli Wang, Yuting Li, Jiaxiong Tan","doi":"10.1186/s40364-024-00686-7","DOIUrl":"10.1186/s40364-024-00686-7","url":null,"abstract":"<p><p>Lung cancer leads in causing cancer-related mortality worldwide, continually posing a significant threat to human health. Current imaging diagnostic techniques, while offering non-invasive detection, suffer from issues such as insufficient sensitivity and the risks associated with radiation exposure. Pathological diagnosis, the gold standard for confirmation, also faces challenges like invasiveness and high costs. In treatment, surgery, radiotherapy, and chemotherapy are the main modalities, each encountering challenges related to precision, environmental adaptability, and side effects. Nanotechnology's advancement provides new solutions for the diagnosis and treatment of lung cancer, promising to enhance diagnostic accuracy and reduce side effects during treatment. This article introduces the main types of nanomaterials used in the field of lung cancer, offering a comprehensive overview of current research on the application of nanotechnology in early screening, diagnosis, treatment, and monitoring of lung cancer, and summarizing ongoing clinical research findings.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"136"},"PeriodicalIF":9.5,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632425","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
Correction: Deciphering LAG-3: unveiling molecular mechanisms and clinical advancements. 更正:解密 LAG-3:揭示分子机制和临床进展。
IF 9.5 2区 医学
Biomarker Research Pub Date : 2024-11-11 DOI: 10.1186/s40364-024-00683-w
Alejandra Martínez-Pérez, Rocío Granda-Díaz, Candelaria Aguilar-García, Christian Sordo-Bahamonde, Segundo Gonzalez
{"title":"Correction: Deciphering LAG-3: unveiling molecular mechanisms and clinical advancements.","authors":"Alejandra Martínez-Pérez, Rocío Granda-Díaz, Candelaria Aguilar-García, Christian Sordo-Bahamonde, Segundo Gonzalez","doi":"10.1186/s40364-024-00683-w","DOIUrl":"https://doi.org/10.1186/s40364-024-00683-w","url":null,"abstract":"","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"135"},"PeriodicalIF":9.5,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632409","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
Validation of a prognostic blood-based sphingolipid panel for men with localized prostate cancer followed on active surveillance. 对接受积极监测的局部前列腺癌男性患者进行基于血液的鞘磷脂预后面板验证。
IF 9.5 2区 医学
Biomarker Research Pub Date : 2024-11-09 DOI: 10.1186/s40364-024-00678-7
Justin R Gregg, Lisa Newcomb, Ranran Wu, Jennifer Dennison, John W Davis, Curtis Pettaway, Louis Pisters, John F Ward, Brian F Chapin, Lisly Chéry, Ahmet Urkmez, Andrew M Fang, Noel Higgason, Patricia Troncoso, Carrie R Daniel, Christopher Logothetis, Timothy C Thompson, Andrew W Hahn, Menghan Liu, Yingye Zheng, Dan W Lin, Samir Hanash, Ehsan Irajizad, Johannes Fahrmann
{"title":"Validation of a prognostic blood-based sphingolipid panel for men with localized prostate cancer followed on active surveillance.","authors":"Justin R Gregg, Lisa Newcomb, Ranran Wu, Jennifer Dennison, John W Davis, Curtis Pettaway, Louis Pisters, John F Ward, Brian F Chapin, Lisly Chéry, Ahmet Urkmez, Andrew M Fang, Noel Higgason, Patricia Troncoso, Carrie R Daniel, Christopher Logothetis, Timothy C Thompson, Andrew W Hahn, Menghan Liu, Yingye Zheng, Dan W Lin, Samir Hanash, Ehsan Irajizad, Johannes Fahrmann","doi":"10.1186/s40364-024-00678-7","DOIUrl":"10.1186/s40364-024-00678-7","url":null,"abstract":"<p><strong>Background: </strong>We previously reported that increases in circulating sphingolipids are associated with elevated risk of biopsy Gleason grade group (GG) upgrading in men on Active Surveillance (AS) for prostate cancer. Here, we aimed to validate these findings and establish a blood-based sphingolipid biomarker panel for identifying men on AS who are at high-risk of biopsy GG upgrading.</p><p><strong>Methods: </strong>Men diagnosed with low- or intermediate-risk prostate cancer in one of two AS cohorts (CANARY PASS and MDACC) were followed for GG upgrading after diagnostic and confirmatory biopsy. The PASS cohort consisted of 544 patients whereas the MDACC Cohort consisted of 697 patients. The number of patients with GG upgrading during course of study follow-up in the PASS and MDACC cohorts were 98 (17.7%) and 133 (19.1%), respectively. Plasmas collected prior to confirmatory biopsy were used for mass spectrometry-based quantitation of 87 unique sphingolipid species. A neural network layer based on 21 sphingolipids was developed in the CANARY PASS cohort for predicting biopsy GG upgrading. Tertile-based thresholds for low-, intermediate-, and high-risk strata were subsequently developed for the sphingolipid panel as well as a model that combined the sphingolipid panel with PSA density and rate of core positivity on diagnostic biopsy. The resultant models and risk thresholds for GG upgrading were validated in the MDACC cohort. Performance was assessed using Cox proportional hazard models, C-index, AUC, and cumulative incidence curves.</p><p><strong>Results: </strong>The sphingolipid panel had a HR (per unit standard deviation increase) of 1.36 (95% CI: 1.07-1.70) and 1.35 (95% CI: 1.11-1.64) for predicting GG biopsy upgrading in the PASS and MDACC cohort, respectively. The model that combined the sphingolipid panel with PSA density and rate of core positivity achieved a HR of 1.63 (95% CI: 1.33-2.00) and 1.44 (1.25-1.66), respectively. Tertile-based thresholds, established in the PASS cohort, were applied to the independent MDACC cohort. Compared to the low-risk group, MDACC patients in the high-risk strata had a GG biopsy upgrade HR of 3.65 (95% CI: 2.21-6.02), capturing 50% of the patients that had biopsy upgrading during study follow-up.</p><p><strong>Conclusions: </strong>The sphingolipid panel is independently associated with GG biopsy upgrading among men in two independent AS cohorts who have previously undergone diagnostic and confirmatory biopsy. The sphingolipid panel, together with clinical factors, provides a potential means for risk stratification to better guide clinical management of men on AS.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"134"},"PeriodicalIF":9.5,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11550521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632427","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
Comparison and combination of mutation and methylation-based urine tests for bladder cancer detection. 膀胱癌检测中基于突变和甲基化的尿液检验的比较与组合。
IF 9.5 2区 医学
Biomarker Research Pub Date : 2024-11-07 DOI: 10.1186/s40364-024-00682-x
Naheema S Gordon, Elspeth K McGuigan, Michaela Ondasova, Jennifer Knight, Laura A Baxter, Sascha Ott, Robert K Hastings, Maurice P Zeegers, Nicholas D James, K K Cheng, Anshita Goel, Minghao Yu, Roland Arnold, Richard T Bryan, Douglas G Ward
{"title":"Comparison and combination of mutation and methylation-based urine tests for bladder cancer detection.","authors":"Naheema S Gordon, Elspeth K McGuigan, Michaela Ondasova, Jennifer Knight, Laura A Baxter, Sascha Ott, Robert K Hastings, Maurice P Zeegers, Nicholas D James, K K Cheng, Anshita Goel, Minghao Yu, Roland Arnold, Richard T Bryan, Douglas G Ward","doi":"10.1186/s40364-024-00682-x","DOIUrl":"10.1186/s40364-024-00682-x","url":null,"abstract":"<p><strong>Background and aims: </strong>Several non-invasive tests for detecting bladder cancer (BC) are commercially available and are based on detecting small panels of BC-associated mutations and/or methylation changes in urine DNA. However, it is not clear which type of biomarker is best, or if a combination of the two is needed. In this study we address this question by taking a 23-gene mutation panel (GALEAS™ Bladder, GB) and testing if adding a panel of methylation markers improves the sensitivity of BC detection.</p><p><strong>Methods: </strong>Twenty-three methylation markers were assessed in urine DNA by bisulphite conversion, multiplex PCR, and next generation sequencing in 118 randomly selected haematuria patients with pre-existing GB data (56 BCs and 62 non-BCs), split into training and test sets. We also analysed an additional 16 GB false-negative urine DNAs.</p><p><strong>Results: </strong>The methylation panel detected bladder cancer in haematuria patients with 69% sensitivity at 96% specificity (test set results, 95% CIs 52-87% and 80-99%, respectively). Corresponding sensitivity and specificity for GB were 92% and 89%. Methylation and mutation markers were highly concordant in urine, with all GB false-negative samples also negative for methylation markers.</p><p><strong>Conclusions and limitations: </strong>Our data show that, with a comprehensive mutation panel, any gains from adding methylation markers are, at best, marginal. It is likely that low tumour content is the commonest cause of false-negative urine test results. Our study does have a limited sample size and other methylation markers might behave differently to the those studied here.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"133"},"PeriodicalIF":9.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607407","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
Advances in CAR-T therapy for central nervous system tumors. 中枢神经系统肿瘤 CAR-T 疗法的进展。
IF 9.5 2区 医学
Biomarker Research Pub Date : 2024-11-06 DOI: 10.1186/s40364-024-00679-6
Delian Zhou, Xiaojian Zhu, Yi Xiao
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