Identification of Biomarkers Related to Tumor Associated Macrophages in Clear Cell Renal Cell Carcinoma with Weighted gene co-expression network analysis

Abstract Background Tumor associated macrophages (TAMs) play an exceedingly important role in tumor microenviroment (TME). However, few studies has reported the specific biomakers and TAM related gene signature in clear cell renal carcinoma (RCC). Herein, our research aims to pick out specific biomakers and construct a TAM related gene prognostic signature in clear cell renal carcinoma. Methods We downloaded clear cell renal carcinoma patients sequence data from The Cancer Genome Atlas (TCGA). Then, we used CIBERSORT and QuanTIseq algorithm to estimate the percentage of immune cell infiltration. Weighted gene co-expression net work analysis (WGCNA) could sort the specific genes related to TAM(M2 macrophage) in clear cell renal carcinoma. In addition, Least Absolute Shrinkage and Selection Operator (LASSO), univariate and multivariate Cox regression were performed to establish a TAM related gene prognostic model in clear cell renal carcinoma patients. At last, single cell sequence from Gene Expression Omnibus (GEO) was also verify the expression of TAM realated genes. Results We found that TAM (M2 macrophage) infiltration was higher than normal tissue, which suggested that TAM may play an vital role in clear cell renal carcinoma progression. Twenty-seven TAM related genes was picked out by using WGCNA. In addition, the six gene prognostic signature which contained: TNFSF8, CD300FL, C3AR1, LAIR1, LY86, RNASE6 was established. We concluded that the riskscore and tumor stage were independent prognostic factors through univariate and multivariate Cox regression analysis. Single cell sequence results show that the six hub genes were all expressed in TAMs. Conclusions In summary, our research discovered that the TAM related genes and constructed a six gene prognostic signature for clear cell renal carcinoma, which may provide a novel insight for targeting therapy in clear cell renal carcinoma.