Moreira Inês B, Rossdam Charlotte, Kaynert Jonas, Beimdiek Julia, Vicente Manuel M, Schmitz Jessica, Großhennig Anika, Oberbeck Astrid, Hoffmann Michèle J, Rosero Moreno Michele E, Steinbach Daniel, Barcena Maria L, Lippka Yannick, Bräsen Jan H, Tezval Hossein, Buettner Falk F R
Institute of Clinical Biochemistry, Hannover Medical School, 30625 Hannover, Germany.
Institute of Clinical Biochemistry, Hannover Medical School, 30625 Hannover, Germany; Proteomics, Institute of Theoretical Medicine, Faculty of Medicine, University of Augsburg, 86159 Augsburg, Germany.
Cell Rep Med. 2025 Aug 19;6(8):102246. doi: 10.1016/j.xcrm.2025.102246. Epub 2025 Jul 23.
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.
糖鞘脂（GSLs）是很有前景的癌症生物标志物。通过使用多重毛细管凝胶电泳结合激光诱导荧光检测（xCGE-LIF），我们对膀胱癌（BC）组织中的GSLs进行了分析，发现与匹配的正常组织相比，新乳糖四糖神经酰胺（nLc4）显著增加（n = 30）。免疫荧光证实了非肌层浸润性膀胱癌（NMIBC）和肌层浸润性膀胱癌（MIBC）中肿瘤特异性nLc4的表达，其与管腔和基底尿路上皮标志物共定位。对配对的组织/尿液样本以及BC细胞系的分析显示，MIBC中nLc4与细胞外囊泡相关的分泌。尿液分析显示，BC患者（n = 16）的nLc4水平高于对照组（n = 50；曲线下面积[AUC]为0.75；准确率为82%）。为了支持临床转化，我们在一个发现队列（n = 18）和一个多中心验证队列（n = 123）中应用了抗nLc4 ELISA。在验证组中，MIBC患者的尿nLc4水平显著升高（AUC为0.78；准确率为64%），并且随着疾病严重程度增加。这些发现支持了尿nLc4作为BC检测的非侵入性生物标志物的潜力。
