Bioinformatics Analysis of Differentially Expressed Rhythm Genes in Liver Hepatocellular Carcinoma

Abstract

Liver Hepatocellular Carcinoma (LIHC), a malignant tumor with high incidence and mortality, is one of the most common cancers in the world. Multiple studies have found that the aberrant expression of rhythm genes is closely related to the occurrence of LIHC. This study aimed to use bioinformatics analysis to identify differentially expressed rhythm genes (DERGs) in LIHC. A total of 563 DERGs were found in LIHC, including 265 downregulated genes and 298 upregulated genes. KEGG pathway enrichment and GO analyses showed that DERGs were significantly enriched in rhythmic and metabolic processes. Survival analysis revealed that high expression levels of CNK1D, CSNK1E, and NPAS2 were significantly associated with the low survival rate in LIHC patients. Through cell experiment verification, the mRNA expression levels of CSNK1D, CSNK1E, and NPAS2 were found to be strongly upregulated, which was consistent with the bioinformatics analysis of LIHC patient samples. A total of 23 nodes and 135 edges were involved in the protein–protein interaction network of CSNK1D, CSNK1E, and NPAS2 genes. Clinical correlation analyses revealed that CSNK1D, CSNK1E, and NPAS2 expression levels were high-risk factors and independently connected with the overall survival rate in LIHC patients. In conclusion, the identification of these DERGs contributes to the exploration of the molecular mechanisms of LIHC occurrence and development and may be used as diagnostic and prognostic biomarkers and molecular targets for chronotherapy in LIHC patients in the future.

Effects and Prognostic Values of Circadian Genes CSNK1E/GNA11/KLF9/THRAP3 in Kidney Renal Clear Cell Carcinoma via a Comprehensive Analysis

“…In recent bioinformatics research, the expression levels of circadian genes were discovered to be closely associated with the tumor microenvironment of non-small cell lung cancer (NSCLC) [ 8 ], and the abnormal expression of circadian genes affected the occurrence and development of glioma by affecting the cell cycle and tumor immune landscape [ 9 ]. Our recent study also identified the differentially expressed rhythm genes CSNK1D/CSNK1E/NPAS2 that were closely linked to the occurrence of liver hepatocellular carcinoma (LIHC) and have the potential to be used as diagnostic biomarkers for patients with LIHC [ 10 ]. However, bioinformatics studies on differentially expressed rhythm genes in KIRC have only rarely been reported [ 11 , 12 ].…”

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

“…Pancancer analysis indicates that the expression of CSNK1D was correlated to shorter DFS time in multiple cancer types, such as COAD and LIHC, and was dysregulated in various cancers, which was consistent previous reports. For example, Liu et al reported that CSNK1D levels are strongly upregulated in HCC samples [ 41 ]. Upregulation of CSNK1D is associated with a poor prognosis for HCC patients.…”

The role of the circadian clock in the development, progression, and treatment of non‐alcoholic fatty liver disease

“…71 Evidence that the clock machinery is gradually hampered and disrupted in liver disease can be appreciated from hepatocellular carcinoma studies as clock gene expression is markedly altered and associated with survival, recurrence, and other important clinical aspects. 72,73 Indeed, chronodisruption is a commonly found process in many-if not all-types of cancer. [74][75][76][77][78] In summary, there is an important gap in our knowledge regarding how the clock behaves under NAFLD/ NASH conditions.…”