Dysregulation of Circadian Clock Genes Associated with Tumor Immunity and Prognosis in Patients with Colon Cancer

Abstract

Early research shows that disrupting the circadian rhythm increases the risk of various cancers. However, the roles of circadian clock genes in colorectal cancer, which is becoming more common and lethal in China, remained to be unclear. In conclusion, the present study has demonstrated that multiple CCGs were dysregulated and frequently mutated in CRC samples by analyzing the TCGA database. The higher expression levels of REV1, ADCYAP1, CSNK1D, NR1D1, CSNK1E, and CRY2 had a strong link with shorter DFS time in CRC patients, demonstrating that CCGs had an important regulatory role in CRC development. Moreover, 513 CRC tumor samples were divided into 3 categories, namely, cluster1 ( n = 428 ), cluster2 ( n = 83 ), and cluster 3 ( n = 109 ), based on the expression levels of the CCGs. Clinical significance analysis showed that the overall survival and disease-free survival of cluster 2 and cluster 3 were significantly shorter than those of cluster 1. The stemness scores in cluster 1 and cluster 2 were significantly higher than those of cluster 3 CRC samples. Clinically, we found that the C3 subtype had significantly higher percentage of T3/T4, N1/N2, and grades III and IV than groups C1 or C2. In addition, we reported that different CRC clusters had significantly different tumor-infiltrating immune cell signatures. Finally, pancancer analysis showed that higher expression of CSNK1D was correlated with shorter DFS time in multiple cancer types, such as COAD and LIHC, and was dysregulated in various cancers. In conclusion, we effectively developed a CCG-related predictive model and opened up new avenues for research into immune regulatory mechanisms and the development of immunotherapy for CRC.

Racial Disparities in the Genetic Landscape of Acute Myeloid Leukaemia from The Cancer Genome Atlas: Insights from a Bioinformatics Analysis

“…This downregulated expression is prevalent in advanced stages of the disease and correlates with invasive carcinoma in cervical cancer [83]. In contrast, elevated ADCYAP1 mRNA levels are linked to a shorter disease-free survival time in colorectal cancer patients [84].…”

A novel circadian cycle-related gene signature for prognosis prediction of patients with breast cancer

“…Further studies have revealed differences in clock gene expression in cancerous tissues compared to healthy tissues. Meanwhile, a number of CCRGs-derived prognostic signature was developed to be effectively used in the prognosis prediction of various cancers, such as colon cancer, [19][20][21] The crucial molecular markers connected to CCRGs in BC, however, have not yet been adequately analyzed.…”