Genetic Association Analysis of Cell Cycle Regulators Reveals YWHAZ Has Prognostic Significance in Prostate Cancer

Cancer Genomics Proteomics. 2020 Mar-Apr;17(2):209-216. doi: 10.21873/cgp.20181.

Abstract

Background/aim: This study aimed to identify the genes that cause biochemical recurrence (BCR) following radical prostatectomy (RP) in men with localized prostate cancer.

Patients and methods: A two-stage genetic association study of 19 single-nucleotide polymorphisms in 11 key cell cycle regulation genes was carried out. BCR-free survival after RP was evaluated in a discovery cohort of 458 patients with prostate cancer, and replication was investigated in another cohort of 185 patients.

Results: A consistent association was found between BCR and rs2290291 (discovery: p=0.008; replication: p=0.029). rs2290291 is located in the tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ), and was predicted to possess a regulatory function that affected YWHAZ expression. Furthermore, YWHAZ expression was frequently up-regulated in advanced tumours, and associated with poorer survival in patients with prostate cancer.

Conclusion: YWHAZ rs2290291 was found to be associated with BCR. YWHAZ may function as a putative oncogene during prostate cancer progression.

Keywords: Cell cycle; YWHAZ; biomarker; prostate cancer; recurrence.

MeSH terms

  • 14-3-3 Proteins / metabolism*
  • Aged
  • Cell Cycle / genetics*
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology

Substances

  • 14-3-3 Proteins
  • YWHAZ protein, human