LAMP3 signature affects cervical cancer progression through autophagy.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.