Gene LY96 is an M2 macrophage‐related biomarker and is associated with immunosuppression in renal cell carcinoma

Lymphocyte Antigen 96 (LY96) was identified as an oncogene in several tumors. However, its role in renal cancer has not been explored. In the study, LY96 is identified abnormally expressed using several public kidney cancer sequencing data. The expression level of LY96 is validated using paired clinical samples. Survival analyses and ROC curves are used to examine its prognostic and diagnostic value. Gene sets enrichment analyses (GSEA) show LY96 might influence immune processes. Then immune infiltration analyses results suggest that LY96 is positively correlated with M2 macrophages infiltration in RCC. Single‐cell data are used to verify its association with macrophages. Moreover, LY96 is positively with various immune scores and might affect the efficacy of immunotherapy. Drug screening results show LY96 might be the target of vemurafenib and etoposide. Further experiments confirm the spatial co‐localization of LY96 and M2, and knocking down LY96 can inhibit M2 polarization. Cell viability experiments indicate that knocking down LY96 would result in a decrease in the resistance of M2 macrophages to etoposide. The study shows LY96 could act as an unfavorable biomarker for RCC and possibly contribute to cancer progression by promoting the infiltration of M2 macrophage. LY96 could be a novel therapeutic target for RCC.