昼夜节律紊乱与肿瘤发生发展密切相关。本研究旨在探讨核心昼夜节律基因与结直肠癌恶性进展的关联。

整合TCGA、Kaplan-Meier Plotter、GEPIA 2.0、TIMER 2.0、cBioPortal和Methsurv等多个数据库资源，系统分析昼夜节律基因与结直肠癌进展的相关性。采用R4.3.2软件进行统计分析，符合正态分布的计量资料以（±s）表示，组间比较采用t检验；不符合正态分布或方差不齐的计量资料采用Wilcoxon秩和检验；计数资料以[例（%）]表示，采用χ²检验或Fisher确切概率法。P<0.05表示差异有统计学意义。

核心昼夜节律基因在结直肠癌与癌旁组织中存在显著差异表达。其中BMAL1、CLOCK、CRY1、NPAS2、NR1D1和PER1/3等高表达与患者不良预后显著相关（P<0.05）。并且这些基因与APC呈强相关，而与MYC、PTEN和TP53等癌基因关联较弱。此外，BMAL1/2、CLOCK、CRY1/2和RORC可影响肿瘤微环境中免疫细胞的浸润状态。CRY1、NPAS2、NR1D1和PER1的高甲基化提示不良预后，而CLOCK和CRY2的脱甲基化则具有保护作用。值得注意的是，昼夜节律基因在结肠癌中的调控作用较直肠癌更为显著，提示可能存在组织特异性调控机制。

昼夜节律基因可以通过调控原癌基因、免疫微环境和DNA甲基化状态影响结直肠癌的恶性进展。并且昼夜节律基因在结肠癌发生发展中的调控作用较直肠癌更为显著。靶向调控昼夜节律的关键基因可能为结肠癌患者提供更具潜力的治疗策略。

Disruption of circadian rhythms is closely associated with tumor occurrence and development. This study aims to explore the association between core circadian rhythm genes and the malignant progression of colorectal cancer.

Multiple database resources such as TCGA, Kaplan-Meier Plotter, GEPIA 2.0, TIMER 2.0, cBioPortal, and Methsurv were integrated to systematically analyze the correlation between circadian rhythm genes and the progression of colorectal cancer. Statistical analysis was performed using R 4.3.2 software. Quantitative data that met normal distribution were expressed as (±s), and comparisons between groups were conducted using t tests; quantitative data that did not meet normal distribution or had unequal variances were analyzed using the Wilcoxon rank sum test; count data were expressed as [cases (%)], and were analyzed using the χ² test or Fisher’s exact probability method. P<0.05 indicated statistically significant differences.

Core circadian rhythm genes showed significant differential expression in colorectal cancer and adjacent tissues. Among them, BMAL1, CLOCK, CRY1, NPAS2, NR1D1, and PER1/3 were highly expressed and significantly correlated with poor prognosis in patients (P<0.05). These genes were strongly correlated with APC, and had a weaker association with oncogenes such as MYC, PTEN, and TP53. Additionally, BMAL1/2, CLOCK, CRY1/2, and RORC could affect the infiltration status of immune cells in the tumor microenvironment. High methylation of CRY1, NPAS2, NR1D1, and PER1 indicated poor prognosis, while demethylation of CLOCK and CRY2 had protective effects. Notably, the regulatory role of circadian rhythm genes in colon cancer was more significant than that in rectal cancer, suggesting the existence of tissue-specific regulatory mechanisms.

Circadian rhythm genes can affect the malignant progression of colorectal cancer by regulating proto-oncogenes, immune microenvironment, and DNA methylation status. Moreover, the regulatory role of circadian rhythm genes in the occurrence and development of colon cancer is more significant than that in rectal cancer. Targeted regulation of key genes of circadian rhythm may provide more promising therapeutic strategies for patients with colon cancer.