Department of Nephrology, Maoming People's Hospital, Maoming 525000, China.
Department of Rehabilitative Medicine, Gaozhou People's Hospital, Maoming 525200, China.
Aging (Albany NY). 2020 Jul 18;12(14):14620-14632. doi: 10.18632/aging.103509.
Kidney renal clear cell carcinoma (KIRC) is one of the most prevalent malignancies with high incidence and mortality. The circadian clock, which is also involved in the regulation of the immune system and tumor microenvironment, is an internal timing system that allows organisms to adjust biological processes and behaviors according to geophysical time.
A wide range of circadian clock genes are epigenetically altered in KIRC, and associated with the overall survival and disease-free survival of patients. SNV analysis revealed missense mutation and splice site to be the most common variant types of circadian clock genes in KIRC. Several circadian clock genes were involved in the regulation of some cancer-related hallmark pathways, including apoptosis and cell cycle pathway. Further, immune infiltrates analysis not only revealed that the expression of circadian clock genes is associated with immune cell infiltrates, but also that somatic copy-number alteration of circadian clock genes could inhibit the immune infiltrates. Moreover, enrichment analysis implied that the circadian clock genes could regulate transcription factor activity and circadian rhythm in KIRC.
Our results demonstrate the potential of chrono-immunotherapy as a candidate option for the management of KIRC.
Multi-omics analysis was performed to comprehensively determine the roles of core circadian clock genes in KIRC.
肾透明细胞癌（KIRC）是最常见的恶性肿瘤之一，具有发病率和死亡率高的特点。生物钟不仅参与免疫系统和肿瘤微环境的调节，还是一种内部计时系统，使生物体能够根据地球物理时间调整生物过程和行为。
在 KIRC 中，广泛的生物钟基因发生了表观遗传改变，并与患者的总生存率和无病生存率相关。SNV 分析显示，错义突变和剪接位点是 KIRC 中生物钟基因最常见的变异类型。一些生物钟基因参与了一些与癌症相关的标志性途径的调节，包括细胞凋亡和细胞周期途径。此外，免疫浸润分析不仅表明生物钟基因的表达与免疫细胞浸润有关，而且生物钟基因的体细胞拷贝数改变可以抑制免疫浸润。此外，富集分析表明，生物钟基因可以调节 KIRC 中的转录因子活性和昼夜节律。
我们的研究结果表明，时间免疫治疗作为 KIRC 治疗的候选方案具有一定的潜力。
进行多组学分析，全面确定核心生物钟基因在 KIRC 中的作用。
