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

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.

SUBMITTER: Yu CC

PROVIDER: S-EPMC7078838 | biostudies-literature | 2020 Mar-Apr

REPOSITORIES: biostudies-literature

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Genetic Association Analysis of Cell Cycle Regulators Reveals <i>YWHAZ</i> Has Prognostic Significance in Prostate Cancer.

Yu Chia-Cheng CC Chen Lih-Chyang LC Lin Wen-Hsin WH Lin Victor C VC Huang Chao-Yuan CY Lu Te-Ling TL Lee Cheng-Hsueh CH Huang Shu-Pin SP Bao Bo-Ying BY

Cancer genomics & proteomics 20200301 2

<h4>Background/aim</h4>This study aimed to identify the genes that cause biochemical recurrence (BCR) following radical prostatectomy (RP) in men with localized prostate cancer.<h4>Patients and methods</h4>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 pati ...[more]

PMID: 32108043

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Project description:BackgroundProstate cancer (PCa) stands as the second most prevalent malignancy impacting male health, and the disease's evolutionary course presents formidable challenges in the context of patient treatment and prognostic management. Charged multivesicular body protein 4 C (CHMP4C) participates in the development of several cancers by regulating cell cycle functions. However, the role of CHMP4C in prostate cancer remains unclear.MethodsIn terms of bioinformatics, multiple PCa datasets were employed to scrutinize the expression of CHMP4C. Survival analysis coupled with a nomogram approach was employed to probe into the prognostic significance of CHMP4C. Gene set enrichment analysis (GSEA) was conducted to interrogate the functional implications of CHMP4C. In terms of cellular experimentation, the verification of RNA and protein expression levels was executed through the utilization of qRT-PCR and Western blotting. Upon the establishment of a cell line featuring stable CHMP4C knockdown, a battery of assays, including Cell Counting Kit-8 (CCK-8), wound healing, Transwell, and flow cytometry, were employed to discern the impact of CHMP4C on the proliferation, migration, invasion, and cell cycle function of PCa cells.ResultsThe expression of CHMP4C exhibited upregulation in both PCa cells and tissues, and patients demonstrating elevated CHMP4C expression levels experienced a notably inferior prognosis. The nomogram, constructed using CHMP4C along with clinicopathological features, demonstrated a commendable capacity for prognostic prediction. CHMP4C knockdown significantly inhibited the proliferation, migration, and invasion of PCa cells (LNcaP and PC3). CHMP4C could impact the advancement of the PCa cell cycle, and its expression might be regulated by berberine. Divergent CHMP4C expression among PCa patients could induce alterations in immune cell infiltration and gene mutation frequency.ConclusionsOur findings suggest that CHMP4C might be a prognostic biomarker in PCa, potentially offering novel perspectives for the advancement of precision therapy for PCa.

Dataset Information

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

Publications

Genetic Association Analysis of Cell Cycle Regulators Reveals <i>YWHAZ</i> Has Prognostic Significance in Prostate Cancer.

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