Research on the circadian clock gene HNF4a in different malignant tumors

Int J Med Sci. 2021 Jan 21;18(6):1339-1347. doi: 10.7150/ijms.49997. eCollection 2021.

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Keywords: HNF4a; circadian clock; malignant tumors; prognosis..

MeSH terms

  • CLOCK Proteins / genetics
  • CLOCK Proteins / metabolism
  • Circadian Clocks / genetics*
  • Datasets as Topic
  • Feedback, Physiological
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Hepatocyte Nuclear Factor 4 / genetics*
  • Hepatocyte Nuclear Factor 4 / metabolism
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / epidemiology
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Staging
  • Neoplasms / diagnosis
  • Neoplasms / genetics*
  • Neoplasms / mortality
  • Neoplasms / pathology
  • Prognosis
  • RNA-Seq

Substances

  • HNF4A protein, human
  • Hepatocyte Nuclear Factor 4
  • CLOCK Proteins