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Int J Med Sci 2017; 14(12):1301-1306. doi:10.7150/ijms.21428 This issue Cite

Research Paper

Cancer Stem Cell Gene Variants Predict Disease Recurrence in Patients Treated with Radical Prostatectomy for Prostate Cancer

Victor C. Lin^1,2✉, Shu-Pin Huang^3,4,5,6, Chao-Yuan Huang^7,8, Chia-Cheng Yu^9,10,11, Hsin-Ling Yin^12,13, Tsung-Yi Huang³, Cheng-Hsueh Lee^3,5, Te-Ling Lu¹⁴, Bo-Ying Bao^14,15,16✉

1. Department of Urology, E-Da Hospital, Kaohsiung, Taiwan;
2. School of Medicine for International Students, I-Shou University, Kaohsiung, Taiwan;
3. Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan;
4. Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;
5. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;
6. Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan;
7. Department of Urology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan;
8. Department of Urology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan;
9. Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan;
10. Department of Urology, School of Medicine, National Yang-Ming University, Taipei, Taiwan;
11. Department of Pharmacy, Tajen University, Pingtung, Taiwan;
12. Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan;
13. Department of Pathology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;
14. Department of Pharmacy, China Medical University, Taichung, Taiwan;
15. Sex Hormone Research Center, China Medical University Hospital, Taichung, Taiwan;
16. Department of Nursing, Asia University, Taichung, Taiwan.

✉ Corresponding authors: Victor C. Lin, Department of Urology, E-Da Hospital, 1 E-Da Road, Jiau-shu Tsuen, Yan-Chau Shiang, Kaohsiung 824, Taiwan. Tel: +886-7-6150011; Fax: +886-7-6150982; E-mail: victorlin0098com.tw; Bo-Ying Bao, Department of Pharmacy, China Medical University, 91 Hsueh-Shih Road, Taichung 404, Taiwan. Tel: +886-4-22053366 ext. 5126; Fax: +886-4-22031075; E-mail: baocmu.edu.tw More

Abstract

Background: Cancer stem cells (CSCs) are involved in tumor progression and drug resistance. We hypothesized that variants in CSC marker genes influence treatment outcomes in prostate cancer.

Methods: Ten potentially functional single nucleotide polymorphisms (SNPs) in seven prostate CSC marker genes, TACSTD2, PROM1, ITGA2, POU5F1, EZH2, PSCA, and CD44, were selected for analysis of their association with disease recurrence by Kaplan-Meier analysis and Cox regression in a cohort of 320 patients with localized prostate cancer receiving radical prostatectomy.

Results: We identified one independent SNP, rs2394882, in POU5F1 that was associated with prostate cancer recurrence (hazard ratio 0.32, 95% confidence interval 0.14-0.71, P = 0.005) after adjustment for known clinical predictors. Further in silico functional analyses revealed that rs2394882 affects POU5F1 expression, which in turn is significantly correlated with prostate cancer aggressiveness and patient prognosis.

Conclusion: Our results suggest that rs2394882 is prognostically relevant in prostate cancer, possibly by modulating the expression of the CSC gene POU5F1.

Keywords: prostate cancer, radical prostatectomy, recurrence, cancer stem cell, single nucleotide polymorphism, POU5F1

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