Abstract:
Circadian rhythms are essential regulators of a multitude of physiological and behavioral processes, such as the metabolism and function of the liver. Circadian rhythms are crucial to liver homeostasis, as the liver is a key metabolic organ accountable for the systemic equilibrium of the body. Circadian rhythm disruption alone is sufficient to cause liver cancer through the maintenance of hepatic metabolic disorder. Although there is evidence linking CRD to hepatocarcinogenesis, the precise cellular and molecular mechanisms that underlie the circadian crosstalk that leads to hepatocellular carcinoma remain unknown. The expression of CRD-related genes in HCC was investigated in this study via bulk RNA transcriptomic analysis and single-cell sequencing. Dysregulated CRD-related genes are predominantly found in hepatocytes and fibroblasts, according to the findings. By using a combination of single-cell RNA sequencing and bulk RNA sequencing analyses, the dysregulated CRD-related genes ADAMTS13, BIRC5, IGFBP3, MARCO, MT2A, NNMT, and PGLYRP2 were identified. The survival analysis using the Kaplan-Meier method revealed a significant correlation between the expression levels of BIRC5 and IGFBP3 and the survival of patients diagnosed with HCC.
摘要:
昼夜节律是许多生理和行为过程的重要调节器,如肝脏的代谢和功能。昼夜节律对肝脏稳态至关重要,因为肝脏是负责身体全身平衡的关键代谢器官。仅昼夜节律中断就足以通过维持肝脏代谢紊乱而导致肝癌。尽管有证据表明CRD与肝癌发生有关,导致肝细胞癌的昼夜节律串扰的确切细胞和分子机制仍然未知。本研究通过批量RNA转录组学分析和单细胞测序研究了CRD相关基因在HCC中的表达。CRD相关基因主要存在于肝细胞和成纤维细胞中。根据调查结果。通过结合使用单细胞RNA测序和批量RNA测序分析,CRD相关基因ADAMTS13、BIRC5、IGFBP3、MARCO、MT2A,NNMT,和PGLYRP2被鉴定。使用Kaplan-Meier方法的生存分析显示BIRC5和IGFBP3的表达水平与诊断为HCC的患者的生存之间存在显着相关性。