ATP8B1: A prognostic prostate cancer biomarker identified via genetic analysis

Author:

Chen Lih‐Chyang1,Huang Shu‐Pin2345,Shih Chieh‐Tien1,Li Chia‐Yang67,Chen Yei‐Tsung8,Huang Chao‐Yuan9,Yu Chia‐Cheng101112,Lin Victor C.1314,Lee Cheng‐Hsueh2,Geng Jiun‐Hung215,Bao Bo‐Ying161718ORCID

Affiliation:

1. Department of Medicine Mackay Medical College New Taipei City Taiwan

2. Department of Urology Kaohsiung Medical University Hospital Kaohsiung Taiwan

3. Graduate Institute of Clinical Medicine, College of Medicine Kaohsiung Medical University Kaohsiung Taiwan

4. Ph.D. Program in Environmental and Occupational Medicine, College of Medicine Kaohsiung Medical University Kaohsiung Taiwan

5. Institute of Biomedical Sciences National Sun Yat‐Sen University Kaohsiung Taiwan

6. Graduate Institute of Medicine, College of Medicine Kaohsiung Medical University Kaohsiung Taiwan

7. Department of Medical Research Kaohsiung Medical University Hospital Kaohsiung Taiwan

8. Department of Life Sciences and Institute of Genome Sciences National Yang Ming Chiao Tung University Taipei Taiwan

9. Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University Taipei Taiwan

10. Division of Urology, Department of Surgery Kaohsiung Veterans General Hospital Kaohsiung Taiwan

11. Department of Urology, School of Medicine National Yang‐Ming University Taipei Taiwan

12. Department of Pharmacy Tajen University Pingtung Taiwan

13. Department of Urology E‐Da Hospital Kaohsiung Taiwan

14. School of Medicine for International Students I‐Shou University Kaohsiung Taiwan

15. Department of Urology Kaohsiung Municipal Hsiao‐Kang Hospital Kaohsiung Taiwan

16. Department of Pharmacy China Medical University Taichung Taiwan

17. Sex Hormone Research Center China Medical University Hospital Taichung Taiwan

18. Department of Nursing Asia University Taichung Taiwan

Abstract

AbstractBackgroundControlling the asymmetric distribution of phospholipids across biological membranes plays a pivotal role in the life cycle of cells; one of the most important contributors that maintain this lipid asymmetry are phospholipid‐transporting adenosine triphosphatases (ATPases). Although sufficient information regarding their association with cancer exists, there is limited evidence linking the genetic variants of phospholipid‐transporting ATPase family genes to prostate cancer in humans.MethodsIn this study, we investigated the association of 222 haplotype‐tagging single‐nucleotide polymorphisms (SNPs) in eight phospholipid‐transporting ATPase genes with cancer‐specific survival (CSS) and overall survival (OS) of 630 patients treated with androgen‐deprivation therapy (ADT) for prostate cancer.ResultsAfter multivariate Cox regression analysis and multiple testing correction, we found that ATP8B1 rs7239484 was remarkably associated with CSS and OS after ADT. A pooled analysis of multiple independent gene‐expression datasets demonstrated that ATP8B1 was under‐expressed in tumor tissues and that a higher ATP8B1 expression was associated with a better patient prognosis. Moreover, we established highly invasive sublines using two human prostate cancer cell lines to mimic cancer progression traits in vitro. The expression of ATP8B1 was consistently downregulated in both highly invasive sublines.ConclusionOur study indicates that rs7239484 is a prognostic factor for patients treated with ADT and that ATP8B1 can potentially attenuate prostate cancer progression.

Funder

China Medical University, Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital

Publisher

Wiley

Subject

Urology,Oncology

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