Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330000, China.
Department of Emergency, The Second Affiliated Hospital of Nanchang University, Nanchang 330000, China.
Comput Math Methods Med. 2022 Jan 25;2022:1709918. doi: 10.1155/2022/1709918. eCollection 2022.
Colon adenocarcinoma (COAD) is a malignancy with a high incidence and is associated with poor quality of life. Dysfunction of circadian clock genes and disruption of normal rhythms are associated with the occurrence and progression of many cancer types. However, studies that systematically describe the prognostic value and immune-related functions of circadian clock genes in COAD are lacking.
Genomic data obtained from The Cancer Genome Atlas (TCGA) database was analyzed for expression level, mutation status, potential biological functions, and prognostic performance of core circadian clock genes in COAD. Their correlations with immune infiltration and TMB/MSI score were analyzed by Spearman's correlation analysis. Pearson's correlation analysis was performed to analyze their associations with drug sensitivity. Lasso Cox regression analysis was performed to construct a prognosis signature. Moreover, an mRNA-miRNA-lncRNA regulatory axis was also detected by ceRNA network.
In COAD tissues, the mRNA levels of , , and were increased, while the mRNA levels of , , , , and were decreased. We also summarized the relative genetic mutation variation landscape. GO and KEGG pathway analyses demonstrated that these circadian clock genes were primarily correlated with the regulation of circadian rhythms and glucocorticoid receptor signaling pathways. COAD patients with high , , and expression had worse prognosis. A prognostic model constructed based on the 9 core circadian clock genes predicted the COAD patients' overall survival with medium to high accuracy. A significant association between prognostic circadian clock genes and immune cell infiltration was found. Moreover, the lncRNA /// regulatory axis in COAD was also detected through a mRNA-miRNA-lncRNA network.
Our results identified , , and as potential prognostic biomarkers for COAD patients and correlated their expression with immune cell infiltration. The lncRNA /// regulatory axis was detected in COAD and might play a vital role in the occurrence and progression of COAD.
结肠腺癌（COAD）是一种发病率较高的恶性肿瘤，与生活质量较差有关。昼夜节律基因功能障碍和正常节律紊乱与许多癌症类型的发生和进展有关。然而，目前缺乏系统描述 COAD 中昼夜节律基因的预后价值和免疫相关功能的研究。
分析来自癌症基因组图谱（TCGA）数据库的基因组数据，以评估 COAD 中核心昼夜节律基因的表达水平、突变状态、潜在生物学功能和预后表现。通过 Spearman 相关性分析评估它们与免疫浸润和 TMB/MSI 评分的相关性。通过 Pearson 相关性分析评估它们与药物敏感性的相关性。通过 Lasso Cox 回归分析构建预后模型。此外，还通过 ceRNA 网络检测 mRNA-miRNA-lncRNA 调控轴。
在 COAD 组织中，mRNA 水平升高，而 mRNA 水平降低。我们还总结了相对的遗传突变变化景观。GO 和 KEGG 通路分析表明，这些昼夜节律基因主要与昼夜节律调节和糖皮质激素受体信号通路相关。COAD 患者中表达水平较高的、和预后较差。基于 9 个核心昼夜节律基因构建的预后模型能够中等至高度准确地预测 COAD 患者的总生存期。发现预后昼夜节律基因与免疫细胞浸润之间存在显著关联。此外，通过 mRNA-miRNA-lncRNA 网络还检测到 COAD 中的 lncRNA /// 调控轴。
我们的研究结果确定、和为 COAD 患者的潜在预后生物标志物，并将其表达与免疫细胞浸润相关联。在 COAD 中检测到 lncRNA /// 调控轴，可能在 COAD 的发生和发展中发挥重要作用。
