This study aimed to investigate the clinical significance, biological functions, and underlying mechanisms of CXCL genes in clear cell renal cell carcinoma (ccRcc) based on patient datasets and pan-cancer analysis. The interaction between CXCL genes in ccRcc and immune components, particularly in relation to neutrophil recruitment and polarization mechanisms, was also evaluated. Furthermore, a risk score was developed using a signature for neutrophil polarization. The role of CXCL2 was assessed through in vitro experiments. Results showed that five CXCL genes (CXCL 2, 5, 9, 10, and 11) were upregulated in renal cancer tissue, while seven genes (CXCL 1, 2, 3, 5, 8, 13, and 14) significantly impacted patient survival. Moreover, CXCL 1, 5, and 13 affected progression-free survival. Besides, differences in mRNA expression and immune components affected renal cancer outcomes. Furthermore, three pairs of CXCL gene-immune cell interactions (CXCL13-CD8+ T cells, CXCL9/10-M1 cells, CXCL1/2/3/8-neutrophils) were identified through single-cell and pan-cancer analysis. A TAN risk score with prognostic value for KIRC patients was constructed using 11 genes and a TAN signature. Neutrophil polarization significantly impacted survival. Notably, CXCL2 was involved in neutrophil recruitment and polarization, thus promoting ccRcc progression. In conclusion, seven prognostic CXCL genes (CXCL 1/2/3/5/8/13/14) for ccRcc patients and three pairs of CXCL gene-immune cell interactions were identified. Furthermore, results showed that CXCL 2 promotes ccRcc progression through neutrophil recruitment and polarization.
Keywords: CXCL genes; TAN phenotype; bioinformatics analysis; clear cell renal cell carcinoma; neutrophil recruitment.