Identification of immune characteristics between different subtypes in kidney renal clear cell carcinoma based on lysosome-related genes to assist immunotherapy.

Previous studies have revealed the essential role of lysosomes in human diseases, including cancer. However, there is a lack of in-depth systematic research on its function in kidney renal clear cell carcinoma (KIRC). In this project, we collected the public dataset of KIRC and selected lysosomal genes tightly linked with survival. Cluster analysis uncovered that these genes possess good classification ability and can divide KIRC patients into multiple subtypes with different survival rates. Enrichment analyses revealed that the main biological processes associated with differentially expressed genes (DEGs) in the two representative subpopulations with the largest survival differences (cluster1 and cluster2) were steroid metabolic process, neutrophil extracellular trap formation, and tyrosine metabolism. The immune-related analysis demonstrated notable differences in immune cell infiltration levels between cluster1 and cluster2 subpopulations of KIRC. More specifically, Tfh and TIL were highly infiltrated in the cluster1, and Type II IFN response, mast cells, and basophils were highly infiltrated in the cluster2. The immunotherapy-related analysis demonstrated that cluster1 may be more sensitive to immunotherapy and more likely to benefit from immunotherapy due to its higher immune checkpoint expression, ESTIMATE score, immune score, and higher immunophenoscore (IPS). In addition, gene mutations occurred in the two subtypes, exhibiting similar mutation patterns between the two subtypes. Finally, based on the cMAP database, we identified some small molecules that may target DEGs between the two subtypes, such as epibatidine, mepyramine, and reboxetine. In conclusion, our investigation unearthed that different subtypes of KIRC patients exhibited different survival outcomes and sensitivity to the immune microenvironment, as well as different responses to immunotherapy. These findings may be beneficial for further mechanistic exploration and therapeutic research of KIRC in the future.