研究Dehydrogenase/Reductase 2(DHRS2)的表現與尿路上皮癌預後之相關性

吳奕儒1、李威明1,2,3、徐偉齊2、林慧惠1,2、吳文正1,2,4、柯宏龍1,2,4,5

高雄醫學大學附設醫院泌尿部1; 高雄醫學大學泌尿學科2;
衛生福利部屏東醫院泌尿科3; 高雄醫學大學醫學研究所4;大同醫院泌尿科5

Decreased Dehydrogenase/Reductase 2(DHRS2) Expression is Associated with Poor Prognosis in Urothelial Carcinoma Patients

Yi-Ru Wu1, Wei-Ming Li 1,2,3, Wei-Chi Hsu 2, Hui-Hui Lin 1,2, Wen-Jeng Wu 1,2,4, Hung-Lung Ke1,2,4,5

1Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

2 Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

3 Department of Urology, Ministry of Health and Welfare Pingtung Hospital, Pingtung, Taiwan.

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

5 Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.

Abstract

Purpose: Dehydrogenase/Reductase 2(DHRS2) is a membrane of the short-chain dehydrogenases/reductases (SDR) superfamily and associates closely with inhibition of cell proliferation, migration and quiescence, as well as locus-specific deletion in several cancer types. However, the role of DHRS2 in Urothelial carcinoma (UC) has not been studied. In this research, we examined the clinical significance of DHRS2 expression in UC.

Materials and methods: 340 Upper tract urothelial carcinoma (UTUC) and 295 Bladder cancer (BC) cases were included in this study. DHRS2 expression was evaluated by immunohistochemistry and the association of DHRS2 expression with different clinicopathological variables was analyzed.

Results: Low DHRS2 expression was significantly associated with higher T stage (p<0.001, p=0.012), high grade (p=0.003, p=0.016), nodal metastasis (p<0.001, p<0.001), lymphovascular invasion (p<0.001, p=0.001) and perineural invasion (p=0.034, p=0.001) in both UTUC and BC cases. In the log-rank test, the low DHRS2 expression was associated with Disease-specific Survival (P<0.0001, P=0.0001) and Metastasis-free Survival (P<0.0001, P<0.0001) in UTUC and BC respectively. This finding was supported by our results using Cox regression analysis, which showed that low DHRS2 expression was an independent predictor of poor Disease-specific Survival (P =0.011, P =0.019) and Metastasis-free Survival (P =0.009, P<0.001) in UTUC and BC separately.

Conclusion: Our study found that DHRS2 is an important indicator of tumor suppressor function of UC progression. Investigating the biological significance and regulation pathway of DHRS2 might be a potential therapeutic target for UC treatment.

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