新乳酸四糖神经酰胺可用于膀胱肿瘤的检测。

IF 10.6 1区医学 Q1 CELL BIOLOGY

Cell Reports Medicine Pub Date : 2025-08-19 Epub Date: 2025-07-23 DOI:10.1016/j.xcrm.2025.102246

Inês B Moreira, Charlotte Rossdam, Jonas Kaynert, Julia Beimdiek, Manuel M Vicente, Jessica Schmitz, Anika Großhennig, Astrid Oberbeck, Michèle J Hoffmann, Michele E Rosero Moreno, Daniel Steinbach, Maria L Barcena, Yannick Lippka, Jan H Bräsen, Hossein Tezval, Falk F R Buettner

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引用次数: 0

摘要

鞘糖脂（GSLs）是一种很有前途的癌症生物标志物。使用激光诱导荧光检测（xcge - liff）的多路毛细管凝胶电泳，我们分析了膀胱癌（BC）组织中的GSLs，发现与匹配的正常组织（n = 30）相比，新乳酸四糖神经酰胺（nLc4）显著增加。免疫荧光证实肿瘤特异性nLc4在非肌肉浸润性BC （NMIBC）和肌肉浸润性BC （MIBC）中表达，与管腔和基底尿路上皮标志物共定位。对配对组织/尿液样本以及BC细胞系的分析显示，nLc4的分泌与MIBC的细胞外囊泡相关。尿谱分析显示，BC患者（n = 16）的nLc4水平高于对照组（n = 50）；曲线下面积[AUC] 0.75；精度为82%)。为了支持临床翻译，我们在发现队列（n = 18）和多中心验证队列（n = 123）中应用了抗nlc4 ELISA。在验证集中，尿nLc4水平在MIBC中显著升高(AUC 0.78；准确率为64%)，并随疾病严重程度的增加而增加。这些发现支持尿nLc4作为BC检测的非侵入性生物标志物的潜力。

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Neolactotetraosylceramide enables urinary detection of bladder cancer.

Glycosphingolipids (GSLs) are promising cancer biomarkers. Using multiplexed capillary gel-electrophoresis with laser-induced fluorescence detection (xCGE-LIF), we profile GSLs in bladder cancer (BC) tissues and find a significant increase in neolactotetraosylceramide (nLc4) compared to matched normal tissue (n = 30). Immunofluorescence confirms tumor-specific nLc4 expression in both non-muscle-invasive BC (NMIBC) and muscle-invasive BC (MIBC), colocalizing with luminal and basal urothelial markers. Analysis of paired tissue/urine samples, along with BC cell lines, reveals secretion of nLc4 associated with extracellular vesicles in MIBC. Urine profiling shows elevated nLc4 levels in BC patients (n = 16) versus controls (n = 50; area under the curve [AUC] 0.75; accuracy 82%). To support clinical translation, we apply an anti-nLc4 ELISA in a discovery cohort (n = 18) and a multi-center validation cohort (n = 123). In the validation set, urinary nLc4 levels are significantly elevated in MIBC (AUC 0.78; accuracy 64%) and increase with disease severity. These findings support the potential of urinary nLc4 as a non-invasive biomarker for BC detection.

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来源期刊

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.