Research Paper Volume 13, Issue 23 pp 25153—25179

Figure 5. The tumor immune infiltration and CRRS. (A) The heatmap showed the GSVA scores of 7 immune and inflammatory gene clusters among the BCa patients with high and low CRRS. (B) 6 of 7 gene clusters were significantly associated with CRRS via Wilcoxon signed-rank tests. (C) The cases with high CRRS carried high Stromal Score, Immune Score, and ESTIMATE Score. (D) The patients in the high-CRRS group had a relatively higher infiltration proportion of CD4 T cells, CD8 T cells, neutrophils, macrophages, and dendritic cells. (E) The CRRS was positively associated with the expression of routine immune checkpoints, which included PD-L1, PD1, LAG3, GAL9, CTLA-4, TIM-3, and TIGIT. (F) The high expression of CXCL9 and CXCL13 was observed in the patients with high CRRS. (G) The Chi-square test indicated the high-CRRS patients were more likely to respond to immunotherapy. (H) CRRS was also a significant biomarker for prognosis in IMvigor 210 cohort. The optimal cut-off was determined by X-tile software. CRRS, circadian rhythm-related score; GSVA, gene set variation analysis; BCa, bladder cancer.