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01-08-2012 | Translational Research and Biomarkers

NDRG2 Is Involved in the Oncogenic Properties of Renal Cell Carcinoma and Its Loss Is a Novel Independent Poor Prognostic Factor After Nephrectomy

Authors: Zhe Long Liang, MD, Kyeongah Kang, PhD, Sukjoon Yoon, PhD, Song Mei Huang, MD, Jae Sung Lim, MD, Jin Man Kim, MD, Jong-Seok Lim, PhD, Hyo Jin Lee, MD

Published in: Annals of Surgical Oncology | Issue 8/2012

Abstract

Background

Although NDRG2 is a candidate tumor suppressor, its exact role in renal cell carcinoma (RCC) is not fully understood. We investigated the functional role of NDRG2 and its clinical relevance in RCC tumorigenesis.

Methods

NDRG2 expression and its clinical implications in clear cell RCC were evaluated. Biological function was assessed by a proliferation assay, anchorage-independent growth assay, and wound healing and transwell migration assays in RCC cell lines overexpressing NDRG2 coupled with an investigation of the effects of NDRG2 expression on the epithelial–mesenchymal transition (EMT).

Results

NDRG2 was differentially expressed in patients with RCC. A loss of NDRG2 was significantly associated with a higher proportion of tumors >10 cm and a high nuclear grade. Furthermore, multivariate analyses indicated that a loss of NDRG2 was an independent poor prognostic factor for patient survival (recurrence-free survival, hazard ratio 7.901; disease-specific survival, hazard ratio 15.395; overall survival, hazard ratio 11.339; P < 0.001 for all parameters). NDRG2 expression inhibited the anchorage-independent growth and migration of RCC cells. NDRG2 expression also modulated the expression of EMT-related genes such as Snail, Slug, and SIP1, and it decreased EMT signaling in RCC cells. Finally, NDRG2 recovered E-cadherin expression in E-cadherin-negative RCC cells.

Conclusions

These results indicate that a lack of NDRG2 is associated with oncogenic properties through the loss of its role as a tumor suppressor, and that NDRG2 is an independent poor prognostic factor predicting survival in clear cell RCC, suggesting that it can serve as a novel prognostic biomarker.

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Title: NDRG2 Is Involved in the Oncogenic Properties of Renal Cell Carcinoma and Its Loss Is a Novel Independent Poor Prognostic Factor After Nephrectomy
Authors: Zhe Long Liang, MD
Kyeongah Kang, PhD
Sukjoon Yoon, PhD
Song Mei Huang, MD
Jae Sung Lim, MD
Jin Man Kim, MD
Jong-Seok Lim, PhD
Hyo Jin Lee, MD
Publication date: 01-08-2012
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 8/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-011-2204-3

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NDRG2 Is Involved in the Oncogenic Properties of Renal Cell Carcinoma and Its Loss Is a Novel Independent Poor Prognostic Factor After Nephrectomy

Abstract

Background

Methods

Results

Conclusions

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Abstract

Background

Methods

Results

Conclusions

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