Chen Chen, Wu Ying, Wu Junlu, Sun Ruixin, Li Yaran, Yao Yiwen, Li Dong
Department of Laboratory Medicine, Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China.
Department of Laboratory Medicine, Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China.
Clin Chim Acta. 2025 Jul 15;575:120376. doi: 10.1016/j.cca.2025.120376. Epub 2025 May 18.
Bladder cancer (BLCA) is a common malignant tumor of the urinary system and is histopathologically divided into high-grade and low-grade BLCA. Accurate diagnosis of BLCA and high-grade BLCA are critical for clinical treatment and early intervention. High-throughput RNA-seq was performed to explore dysregulated long non-coding RNAs (lncRNAs) in urinary extracellular vesicles (uEVs) from BLCA patients, and their expression levelswereexamined inalarge cohort of uEVs samples using qRT-PCR. Weexaminedthe expressionlevels and subcellular localization of the lncRNAs in BLCA tissues andcelllines. We analyzed the correlation between the expression levels of lncRNAs in uEVs and clinical parameters and assessed their clinical value as diagnostic biomarkers for BLCA and high-grade BLCA using receiver operating characteristic (ROC) curve. Through high-throughput RNA-seq, we identified several dysregulated lncRNAs (MALAT1, SCARNA10, LINC00963 and LINC01578) in uEVs from BLCA patients. The lncRNAs were significantly upregulated in uEVs of BLCA patients, however with varying expression levels in tissues and cell lines. The lncRNAsarepredominantlylocalizedinthe nucleus of BLCA cell lines. Elevated expression levels of the lncRNAs were associated with adverse factors, including higher tumor grade and larger tumor diameter. ROCcurve analysis showed thatthe combination of four lncRNAs in uEVs and the existing marker nuclear matrix protein 22 provided substantial diagnostic value for BLCA and high-grade BLCA, with area under curve values of 0.900 and 0.917, respectively. The lncRNA panel derived from uEVs may serve as a promising non-invasive biomarker for diagnosing BLCA and high-grade BLCA.
膀胱癌（BLCA）是泌尿系统常见的恶性肿瘤，在组织病理学上分为高级别和低级别BLCA。准确诊断BLCA和高级别BLCA对临床治疗和早期干预至关重要。进行了高通量RNA测序，以探索BLCA患者尿液细胞外囊泡（uEVs）中失调的长链非编码RNA（lncRNAs），并使用qRT-PCR在大量uEVs样本队列中检测它们的表达水平。我们检测了lncRNAs在BLCA组织和细胞系中的表达水平及亚细胞定位。我们分析了uEVs中lncRNAs表达水平与临床参数之间的相关性，并使用受试者工作特征（ROC）曲线评估它们作为BLCA和高级别BLCA诊断生物标志物的临床价值。通过高通量RNA测序，我们在BLCA患者的uEVs中鉴定出几种失调的lncRNAs（MALAT1、SCARNA10、LINC00963和LINC01578）。这些lncRNAs在BLCA患者的uEVs中显著上调，但在组织和细胞系中的表达水平有所不同。这些lncRNAs主要定位于BLCA细胞系的细胞核中。lncRNAs表达水平升高与不良因素相关，包括更高的肿瘤分级和更大的肿瘤直径。ROC曲线分析表明，uEVs中四种lncRNAs与现有标志物核基质蛋白22的组合对BLCA和高级别BLCA具有显著的诊断价值，曲线下面积值分别为0.900和0.917。源自uEVs的lncRNA组合可能是诊断BLCA和高级别BLCA的有前景的非侵入性生物标志物。
