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LRRC15-SCG5在细胞外基质蛋白结合中作为尿路上皮癌预后标志物的作用。

The role of LRRC15-SCG5 in ECM protein binding as a prognostic signature for urothelial carcinoma.

作者信息

Dong Shao-Wei, Chen Chih-Heng, Tzou Kai-Yi, Hu Su-Wei, Wu Chia-Chang, Li Chien Hsiu

机构信息

Department of Urology, Shuang Ho Hospital, Taipei Medical University New Taipei, Taiwan.

Taipei Medical University (TMU) Research Center of Urology and Kidney, Taipei Medical University Taipei, Taiwan.

出版信息

Am J Cancer Res. 2025 May 25;15(5):2301-2318. doi: 10.62347/ABZG4705. eCollection 2025.

Abstract

Membrane-bound LRRC15 facilitates communication with adjacent cells by interacting with extracellular molecules, yet its role in urothelial carcinoma remains undefined. A systematic analysis of clinicopathological transcriptome profiles of urothelial carcinoma patients reveals that dysregulated levels of LRRC15 are associated with tumor malignancy features and poor prognosis. A clinically based molecular simulation model highlights potential mechanisms whereby LRRC15 mediates urothelial carcinoma cell motility and growth, primarily through the extracellular matrix organization pathway. Further molecular interaction mapping identifies SCG5 as a novel molecule linking to LRRC15 via protein-protein interactions, positively correlating with advanced pathological features and worse prognosis in urothelial carcinoma patients. Kaplan-Meier plotter results indicate that the LRRC15/SCG5 axis can serve as a prognostic marker for low survival rates in both non-muscle invasive and muscle-invasive bladder cancer. Molecules affected by the LRRC15/SCG5 axis in bladder cancer and upper tract urothelial carcinoma contribute to signatures of poor prognosis in urothelial carcinoma. These findings support targeting the LRRC15/SCG5 axis as a potential therapeutic strategy to intervene in urothelial carcinoma progression.

摘要

膜结合型LRRC15通过与细胞外分子相互作用促进与相邻细胞的通讯,但其在尿路上皮癌中的作用仍不明确。对尿路上皮癌患者临床病理转录组图谱的系统分析表明,LRRC15水平失调与肿瘤恶性特征和预后不良相关。一个基于临床的分子模拟模型突出了LRRC15介导尿路上皮癌细胞运动和生长的潜在机制,主要通过细胞外基质组织途径。进一步的分子相互作用图谱确定SCG5是一种通过蛋白质-蛋白质相互作用与LRRC15相连的新分子,与尿路上皮癌患者的晚期病理特征和更差的预后呈正相关。Kaplan-Meier绘图仪结果表明,LRRC15/SCG5轴可作为非肌层浸润性和肌层浸润性膀胱癌低生存率的预后标志物。在膀胱癌和上尿路尿路上皮癌中受LRRC15/SCG5轴影响的分子促成了尿路上皮癌预后不良的特征。这些发现支持将LRRC15/SCG5轴作为干预尿路上皮癌进展的潜在治疗策略。

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