Research on the circadian clock gene HNF4a in different malignant tumors

Meng-Jun Qiu1, Li Zhang1, Xie-Fan Fang2

  • 1Division of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430077, China.

Insights

Hepatocyte nuclear factor 4-alpha (HNF4a) exhibits varied roles in cancer. While high HNF4a expression correlates with better prognosis in several cancers, it indicates a poor prognosis in lung squamous cell carcinoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Chronobiology

Background:

  • Circadian rhythm, regulated by core clock genes, influences human metabolism and physiology.
  • Aberrant expression of clock genes is linked to various cancers, acting as either pro-cancer or anti-cancer factors.
  • Hepatocyte nuclear factor 4-alpha (HNF4a) possesses characteristics of clock proteins involved in negative feedback loops.

Purpose of the Study:

  • To investigate the function of HNF4a as a circadian clock gene in malignant tumors.
  • To explore the prognostic significance of HNF4a across different cancer types.

Main Methods:

  • Utilized The Cancer Genome Atlas (TCGA) database for RNA-sequencing and clinical data from twenty malignant tumors.
  • Integrated standardized HNF4a RNA-seq data with clinicopathological information to analyze patient prognosis.

Main Results:

  • HNF4a expression significantly impacts prognosis in bladder cancer (BLCA), kidney renal clear cell carcinoma (KIRC), lung squamous cell carcinoma (LUSC), and rectal adenocarcinoma (READ).
  • High HNF4a expression correlates with favorable prognosis in BLCA, KIRC, and READ, but with poor prognosis in LUSC.
  • HNF4a is associated with tumor stage, T stage, and lymph node status specifically in BLCA.

Conclusions:

  • HNF4a demonstrates differential roles across various malignancies.
  • Aberrant HNF4a expression is closely linked to the biological characteristics of BLCA.
  • Low HNF4a expression may serve as a prognostic biomarker for metastasis, recurrence, and overall outcome in BLCA.

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