Expression profile and prognostic value of the circadian clock in clear cell renal cell carcinoma

Abstract

Background A growing number of studies indicate that the circadian clock is a crucial regulator of tumorigenesis and the progression of diverse cancers. Clear cell renal cell carcinoma (ccRCC) is an extremely malignant tumor with a poor prognosis. However, the implications of circadian clock genes in ccRCC remain poorly understood.Methods We evaluated the expression pattern of circadian clock genes and their prognostic significance in ccRCC. Cluster analysis and Gene set enrichment analysis (GSEA) were used to assess the biological mechanisms of subgroups. Cox regression, GO and KEGG enrichment analysis, ESTIMATE, CIBERSORTx, and ceRNA networks were utilized to investigate the prognostic significance and underlying mechanisms of the circadian clock in ccRCC.Results We found a strong correlation between 17 circadian clock genes and ccRCC prognosis. Eight circadian clock genes were chosen to construct a new risk signature that categorized all ccRCC patients as low- or high-risk. The low-risk group had significantly greater chances of survival than the high-risk group (P < 0.001). In conjunction with clinical characteristics, the risk score was identified as an independent prognostic factor for patients with ccRCC. Immune infiltration analysis revealed that T cells CD4 memory resting, Macrophages M1, Mast cells resting, Dendritic cells resting, and Monocytes were significantly higher in the low-risk subgroup, whereas the high-risk subgroup had a greater proportion of T cells regulatory (Tregs), which was consistent with the pathways identified by ssGSEA. Finally, the ceRNA network was constructed successfully, and the significantly low expression levels of FBXL3 and HLF were verified in human RCC tissues.Conclusion Our research uncovered the crucial role of circadian clock genes in tumor immunity and identified a risk signature as a promising biomarker for predicting the prognosis of patients with ccRCC. Our findings lay the groundwork for future research focusing on the circadian clock and immune microenvironment to improve the prognosis and immunotherapy responses in ccRCC.