Ji Haizhou, Zheng Jianfeng, Liu Li, Liu Qinying, Cai Xintong, Ji Liyan, Sun Yang
Department of Gynecology, Fujian Cancer Hospital, Clinical Oncology School of Fujian Medical University, Fuzhou, 350014, China.
Geneplus-Beijing Institute, Beijing, 10000, China.
BMC Cancer. 2025 Jul 24;25(1):1206. doi: 10.1186/s12885-025-14596-w.
Lysosomes are monolayer membrane-encapsulated organelles containing acid hydrolases, crucial for intracellular substance breakdown and cellular homeostasis. They are also involved in autophagy. Although autophagy is linked to cancer, the role of lysosome-related genes in cervical cancer prognosis remains unclear. This study aimed to develop a prognostic model for cervical cancer based on lysosome-related genes and explore its applications in the tumor microenvironment, radiotherapy prognosis, and clinical pharmacology.
We identified differentially expressed lysosome-related genes in cervical cancer and normal tissues using the TCGA database. A prognostic model was constructed using LASSO-Cox regression, validated with ROC curves and PCA analysis, and further verified using the GEO dataset GSE63514. In vitro and in vivo experiments were conducted to explore key genes, and their biological significance and pharmacological potential were analyzed.
A five-gene (AP1B1, DNASE2, LAMP3, NPC1, and LAPTM4A) lysosome-associated prognostic model was developed. LAMP3 was identified as the most differentially expressed gene. Knockdown of LAMP3 significantly reduced cervical cancer cell migration and invasion through lysosomal and autophagic pathways. Daidzein was found to have high binding affinity for LAMP3, suggesting its therapeutic potential.
Lysosome-related gene modeling has significant clinical value. LAMP3 knockdown inhibits cervical cancer progression by reducing autophagy and lysosomal function. Daidzein shows potential as a novel therapeutic agent. However, further validation in larger cohorts is needed due to the limited sample size in this study.
溶酶体是单层膜包裹的细胞器，含有酸性水解酶，对细胞内物质分解和细胞稳态至关重要。它们也参与自噬。尽管自噬与癌症有关，但溶酶体相关基因在宫颈癌预后中的作用仍不清楚。本研究旨在基于溶酶体相关基因开发一种宫颈癌预后模型，并探索其在肿瘤微环境、放疗预后和临床药理学中的应用。
我们使用TCGA数据库鉴定了宫颈癌组织和正常组织中差异表达的溶酶体相关基因。使用LASSO-Cox回归构建预后模型，通过ROC曲线和PCA分析进行验证，并使用GEO数据集GSE63514进一步验证。进行体外和体内实验以探索关键基因，并分析其生物学意义和药理潜力。
建立了一个包含五个基因（AP1B1、DNASE2、LAMP3、NPC1和LAPTM4A）与溶酶体相关的预后模型。LAMP3被确定为差异表达最显著的基因。敲低LAMP3可通过溶酶体和自噬途径显著降低宫颈癌细胞的迁移和侵袭。发现大豆苷元对LAMP3具有高结合亲和力，表明其治疗潜力。
溶酶体相关基因建模具有重要的临床价值。敲低LAMP3可通过降低自噬和溶酶体功能抑制宫颈癌进展。大豆苷元显示出作为新型治疗药物的潜力。然而，由于本研究样本量有限，需要在更大队列中进一步验证。
