研究概要
本研究为LAMP5促进膀胱癌进展的分子机制提供了见解,并为治疗干预和临床管理提供了潜在靶点。
中文摘要
溶酶体相关膜蛋白家族成员5(LAMP5)是近年来发现的LAMP家族成员,已被认为与多种癌症类型的不良预后相关;然而,其确切的致癌机制仍不清楚。本研究利用多个数据集系统研究了LAMP5的致癌和免疫学功能。LAMP5表达在多种癌症中显著失调,突显了其作为诊断和预后生物标志物的潜力。GSVA表明,LAMP5表达可能与增强的细胞增殖和肿瘤侵袭潜能相关;它也可能与抗肿瘤免疫反应的改变相关。使用多数据库分析的免疫浸润分析显示,高LAMP5表达与免疫细胞浸润增加相关,包括自然杀伤T细胞和肿瘤相关成纤维细胞,并伴有免疫检查点分子和趋化因子的上调。使用多个免疫治疗队列的验证表明,LAMP5表达升高可能与免疫治疗疗效降低相关。在膀胱癌中的聚焦研究显示,LAMP5通过调控FBXW11/p27轴促进增殖。这些发现将LAMP5鉴定为一种在膀胱癌中具有预后和治疗相关性的多功能癌蛋白。本研究为LAMP5促进膀胱癌进展的分子机制提供了见解,并为治疗干预和临床管理提供了潜在靶点。
展开英文摘要原文
Lysosomal associated membrane protein family member 5 (LAMP5), a recently identified member of the LAMP family, has been associated with poor prognosis in multiple cancer types; however, its precise oncogenic mechanisms remain unclear. This study systematically investigated the oncogenic and immunological functions of LAMP5 using multiple datasets. LAMP5 expression was significantly dysregulated in various cancers, highlighting its potential as a diagnostic and prognostic biomarker. GSVA indicated that LAMP5 expression is likely associated with enhanced cell proliferation and tumor invasive potential; it may also be correlated with alterations in anti-tumor immune responses. Immune infiltration analyses using Multi-database analyses revealed that high LAMP5 expression was associated with increased infiltration of immune cells including natural killer T cells and tumor-associated fibroblasts, accompanied by upregulation of immune checkpoint molecules and chemokines. Validation using various immunotherapy cohorts showed that elevated LAMP5 expression may be linked to reduced immunotherapy efficacy. A focused investigation in bladder cancer revealed that LAMP5 facilitates proliferation via regulation of the FBXW11/p27 axis. These findings identify LAMP5 as a multifunctional oncoprotein with both prognostic and therapeutic relevance in bladder cancer. This study provides insights into the molecular mechanisms by which LAMP5 promotes bladder cancer progression and offers potential targets for therapeutic intervention and clinical management.
论文信息
- 作者
- Lin Z、Zhao K、Wang S、Liu J、Liu Y、Qiang K、Huang M、Sun N
- 第一作者单位
- Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.China
- 通讯作者单位
- Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. jinhonglei@wmu.edu.cn.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Apoptosis : an international journal on programmed cell death2026 Feb 9