Annals of Surgical Oncology

, Volume 21, Supplement 4, pp 538–545 | Cite as

DHCR24 is an Independent Predictor of Progression in Patients with Non-Muscle-Invasive Urothelial Carcinoma, and Its Functional Role is Involved in the Aggressive Properties of Urothelial Carcinoma Cells

  • Geun Taek Lee
  • Yun-Sok Ha
  • Yeon Suk Jung
  • Sung-Kwon Moon
  • Ho Won Kang
  • Ok-Jun Lee
  • Jae Young Joung
  • Yung Hyun Choi
  • Seok-Joong Yun
  • Wun-Jae Kim
  • Isaac Yi Kim
Translational Research and Biomarkers

Abstract

Purpose

The DHCR24 gene that encodes 3b-hydroxysterol Δ24-reductase, an oxidoreductase involved in cholesterol biosynthesis, has been identified as a progression-related gene based on the quantitative real-time PCR (qPCR) gene signature. Here, the functional role of DHCR24 and its clinical relevance in non-muscle-invasive urothelial carcinoma (NMIUC) were investigated.

Methods

Primary NMIUC tissue specimens (n = 162) were analyzed by qPCR. Immunohistochemical staining was also performed on 63 subsets of NMIUC tissues. The present study was also undertaken in order to verify the effect of DHCR24 on human urothelial carcinoma cells.

Results

The mRNA expression levels of DHCR24 were significantly higher for patients in with higher grades of tumors than for those with lower grades of tumors (P = 0.003). Kaplan–Meier estimates revealed significant differences in the time to progression between low- and high-mRNA expression groups (log-rank test, P < 0.001). Multivariate Cox regression analysis revealed that the level of DHCR24 expression is an independent predictor of progression (hazard ratio, 5.464; 95 % confidence interval, 1.746–17.099; P = 0.004). The results of immunohistochemical staining were generally concordant with mRNA expression levels. Enforced expression of DHCR24 caused proliferation, adhesion, and migration, while DHCR24 loss resulted in slower proliferation and a reduction in cell viabilities compared with control cells.

Conclusions

DHCR24 was found to be closely associated with progression among patients with NMIUC and showed aggressive properties in human UC cells.

Keywords

HT1376 Cell SW780 Cell Urothelial Carcinoma Desmosterol U18666A 

Notes

Acknowledgment

This work was supported in part by a grant from the National Cancer Institute (P30CA072720). It was also supported in part by generous grants from the Tanzman Foundation, Jon Runyan’s Score for the Cure, and by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education Science and Technology (2008–0062611) and supported by a grant from the Next-Generation BioGreen 21 Program (PJ009621), Rural Development Administration, Republic of Korea. The biospecimens for this study were provided by the Chungbuk National University Hospital, a member of the National Biobank of Korea, which is supported by the Ministry of Health, Welfare and Family Affairs. All samples derived from the National Biobank of Korea were obtained with informed consent under institutional review board–approved protocols.

Disclosure

The authors declare no conflict of interest.

Supplementary material

10434_2014_3560_MOESM1_ESM.tif (30 kb)
Fig. S1 Receiver operating characteristics (ROC) curve generated from DHCR24 expression in non-muscle-invasive urothelial carcinoma for the prediction of progression (sensitivity 63.2 %, specificity 74.1 %) Supplementary material 1 (TIFF 29 kb)
10434_2014_3560_MOESM2_ESM.tif (30 kb)
Fig. S2 Effect of DHCR24 expression on progression of NMIUC (log-rank test, P = 0.005) Supplementary material 2 (TIFF 30 kb)
10434_2014_3560_MOESM3_ESM.tif (124 kb)
Fig. S3 Differentially expressed mRNA levels of DHCR24 in various UC cell lines Supplementary material 3 (TIFF 124 kb)
10434_2014_3560_MOESM4_ESM.tif (20 kb)
Fig. S4 DHCR24 knockdown by shRNAs and inhibitor-suppressed oncogenesis. a Proliferation of knockdown cell lines was compared with control cells in TCCSUP (left panel) and SW780 (right panel). b U18666A and cell count. There were significant decreases in cell numbers in a dose-dependent manner Supplementary material 4 (TIFF 19 kb)
10434_2014_3560_MOESM5_ESM.tif (16 kb)
Fig. S5 The effect of U18666A on HT1376 cells showing no significant changes in cell numbers Supplementary material 5 (TIFF 15 kb)
10434_2014_3560_MOESM6_ESM.docx (13 kb)
Supplementary material 6 (DOCX 13 kb)
10434_2014_3560_MOESM7_ESM.docx (15 kb)
Supplementary material 7 (DOCX 14 kb)
10434_2014_3560_MOESM8_ESM.docx (16 kb)
Supplementary material 8 (DOCX 15 kb)

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Copyright information

© Society of Surgical Oncology 2014

Authors and Affiliations

  • Geun Taek Lee
    • 1
  • Yun-Sok Ha
    • 1
    • 2
  • Yeon Suk Jung
    • 1
  • Sung-Kwon Moon
    • 3
  • Ho Won Kang
    • 2
  • Ok-Jun Lee
    • 4
  • Jae Young Joung
    • 5
  • Yung Hyun Choi
    • 6
  • Seok-Joong Yun
    • 2
  • Wun-Jae Kim
    • 2
  • Isaac Yi Kim
    • 1
  1. 1.Section of Urologic Oncology and Dean and Betty Gallo Prostate Cancer Center, Rutgers Cancer Institute of New JerseyRutgers, The State University of New JerseyNew BrunswickUSA
  2. 2.Department of UrologyChungbuk National University College of MedicineCheongjuKorea
  3. 3.Department of Food Science and TechnologyChung-Ang UniversityAnsungRepublic of Korea
  4. 4.Department of PathologyChungbuk National University College of MedicineCheongjuKorea
  5. 5.Department of Urology, Center for Prostate CancerNational Cancer CenterGoyangKorea
  6. 6.Department of BiochemistryDongeui University College of Oriental MedicinePusanKorea

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