Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Mar-Apr;17(2):209-216.
doi: 10.21873/cgp.20181.

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

Chia-Cheng Yu  1   2   3 , Lih-Chyang Chen  4 , Wen-Hsin Lin  5 , Victor C Lin  6   7 , Chao-Yuan Huang  8 , Te-Ling Lu  5 , Cheng-Hsueh Lee  9   10 , Shu-Pin Huang  11   10   12   13 , Bo-Ying Bao  14   15   16
Affiliations

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

Chia-Cheng Yu et al. Cancer Genomics Proteomics. 2020 Mar-Apr.

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.

PubMed Disclaimer

Conflict of interest statement

The Authors declare that they have no conflicts of interest in regard to this study.

Figures

Figure 1
Figure 1. Kaplan–Meier survival curves of biochemical recurrence-free survival, according to YWHAZ rs2290291 genotypes in the (A) discovery set, (B) replication set, and (C) combined analysis. Numbers in parentheses indicate the number of patients.
Figure 2
Figure 2. Functional analyses of YWHAZ rs2290291. (A) Forest plot for meta-analysis of the correlation between rs2290291 and YWHAZ expression in 9745 tissue samples from the GTEx dataset. Correlation of YWHAZ expression with prostate cancer progression. (B) High Gleason score and (C) high stage prostate cancers displayed significantly higher mRNA expression. Increased YWHAZ expression was significantly associated with poor (D) overall survival in the TCGA dataset, (E) overall survival in the dataset from Sboner et al. (2010), and (F) BCR-free survival in the dataset from Taylor et al. (2010). Patients were classified into low- and high-risk groups by an optimization algorithm for the minimum p-value. Numbers in parentheses indicate the number of patients. Rho: Spearman’s rank correlation coefficient.
See this image and copyright information in PMC

References

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7–34. PMID: 30620402. DOI: 10.3322/caac.21551. - PubMed
    1. Freedland SJ, Humphreys EB, Mangold LA, Eisenberger M, Dorey FJ, Walsh PC, Partin AW. Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy. JAMA. 2005;294(4):433–439. PMID: 16046649. DOI: 10.1001/jama.294.4.433. - PubMed
    1. Roehl KA, Han M, Ramos CG, Antenor JA, Catalona WJ. Cancer progression and survival rates following anatomical radical retropubic prostatectomy in 3,478 consecutive patients: Long-term results. J Urol. 2004;172(3):910–914. PMID: 15310996. DOI: 10.1097/01.ju.0000134888.22332.bb. - PubMed
    1. Morgan DO. Principles of cdk regulation. Nature. 1995;374(6518):131–134. PMID: 7877684. DOI: 10.1038/374131a0. - PubMed
    1. Elledge SJ. Cell cycle checkpoints: Preventing an identity crisis. Science. 1996;274(5293):1664–1672. PMID: 8939848. DOI: 10.1126/science.274.5293.1664. - PubMed