Autophagy-related gene LAPTM4B promotes the progression of renal clear cell carcinoma and is associated with immunity

Abstract

Renal cell carcinoma (RCC) is a common urologic disease. Currently, surgery is the primary treatment for renal cancer; immunotherapy is not as effective a treatment strategy as expected. Hence, understanding the mechanism in the tumor immune microenvironment (TME) and exploring novel immunotherapeutic targets are considered important. Recent studies have demonstrated that autophagy could affect the immune environment of renal cell carcinoma and induce proliferation and apoptosis of cancer cells. By comparing lysosomal genes and regulating autophagy genes, we identified the LAPTM4B gene to be related to RCC autophagy. By analyzing the TCGA-KIRC cohort using bioinformatics, we found M2 macrophages associated with tumor metastasis to be significantly increased in the immune microenvironment of patients with high expression of LAPTM4B. GO/KEGG/GSEA/GSVA results showed significant differences in tumor autophagy- and metastasis-related pathways. Single-cell sequencing was used to compare the expression of LAPTM4B in different cell types and obtain the differences in lysosomal and autophagy pathway activities in different ccRCC cells. Subsequently, we confirmed the differential expression of LAPTM4B in renal cell carcinoma of different Fuhrman grades using western blotting. Downregulation of LAPTM4B expression significantly reduced the proliferation of renal cell carcinoma cells and promoted cell apoptosis through cell experiments. Overall, our study demonstrated that the autophagy-related gene LAPTM4B plays a critical role in the TME of RCC, and suggested that LAPTM4B is a potential therapeutic target for RCC immunotherapy.