Division of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430077, China.
Charles River Laboratories, Inc., 6995 Longley Lane, Reno NV 89511.
Int J Med Sci. 2021 Jan 21;18(6):1339-1347. doi: 10.7150/ijms.49997. eCollection 2021.
The circadian rhythm is produced by multiple feedback loops formed by the core clock genes after transcription and translation, thus regulating various metabolic and physiological functions of the human body. We have shown previously that the abnormal expression of 14 clock genes is related closely to the occurrence and development of different malignant tumors, and these genes may play an anti-cancer or pro-cancer role in different tumors. HNF4a has many typical properties of clock proteins involved in the clock gene negative feedback loop regulation process. We need to explore the function of HNF4a as a circadian clock gene in malignant tumors further. We used The Cancer Genome Atlas (TCGA) database to download the clinicopathological information of twenty malignant tumors and the corresponding RNA-seq data. The HNF4a RNA-seq data standardized by R language and clinical information were integrated to reveal the relationship between HNF4a and prognosis of patients. Analysis of TCGA data showed that the prognosis of HNF4a was significantly different in BLCA, KIRC, LUSC, and READ. High HNF4a expression is correlated with good prognosis in BLCA, KIRC, and READ but poor prognosis in LUSC. However, HNF4a was associated with the stages, T stages, and lymph node status only in BLCA. HNF4a plays different roles in different malignancies, and the abnormal expression of HNF4a has a great correlation with the biological characteristics of BLCA. The low expression of HNF4a could be a reference index for the metastasis, recurrence, and prognosis of BLCA.
昼夜节律是由核心时钟基因转录和翻译后形成的多个反馈环产生的,从而调节人体的各种代谢和生理功能。我们之前已经表明,14 个时钟基因的异常表达与不同恶性肿瘤的发生和发展密切相关,这些基因在不同的肿瘤中可能发挥抗癌或致癌作用。HNF4a 具有时钟蛋白的许多典型特性,参与时钟基因负反馈环调节过程。我们需要进一步探讨 HNF4a 作为昼夜节律基因在恶性肿瘤中的功能。
我们使用癌症基因组图谱(TCGA)数据库下载了二十种恶性肿瘤的临床病理信息和相应的 RNA-seq 数据。用 R 语言对 HNF4a RNA-seq 数据进行标准化,并整合临床信息,以揭示 HNF4a 与患者预后之间的关系。TCGA 数据分析表明,BLCA、KIRC、LUSC 和 READ 中 HNF4a 的预后有显著差异。BLCA、KIRC 和 READ 中 HNF4a 高表达与预后良好相关,但 LUSC 中与预后不良相关。然而,HNF4a 仅与 BLCA 的分期、T 分期和淋巴结状态有关。
HNF4a 在不同的恶性肿瘤中发挥不同的作用,HNF4a 的异常表达与 BLCA 的生物学特性有很大的相关性。HNF4a 低表达可能是 BLCA 转移、复发和预后的参考指标。