The Metastasis Suppressor, N-myc Downregulated Gene 1 (NDRG1), is a Prognostic Biomarker for Human Colorectal Cancer

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Jul 23

PMID 23874544

Citations 35

Authors

Zhihai Mao

Jing Sun

Bo Feng

Junjun Ma

Lu Zang

Feng Dong

Daohai Zhang

Minhua Zheng

Affiliations

Soon will be listed here.

Abstract

Metastasis remains to be one of the most prevalent causes leading to poor long-term survival of colorectal cancer (CRC) patients. The clinical significances of tumor metastatic suppressor, N-myc downregulated gene 1 (NDRG1), have been inconsistently reported in a variety of cancerous diseases. In this study with 240 CRC clinical specimens, we showed that NDRG1 expression was significantly decreased in most of CRC tissues compared to the paired non-tumor counterparts. Statistical analysis revealed a significant inverse correlation of NDRG1 expression with tumor stage, differentiation status and metastasis. Compared with NDRG1-negative group, NDRG1-positve group had better disease-free/overall survival (p = 0.000) over 5 years' follow-up. Furthermore, NDRG1 was considered to be an independent prognostic factor for overall survival (p = 0.001) and recurrence (p = 0.003). Our study concludes that NDRG1 is a novel favorable predictor for the prognosis in CRC patients.

Citing Articles

Metixene is an incomplete autophagy inducer in preclinical models of metastatic cancer and brain metastases.

Fares J, Petrosyan E, Kanojia D, Dmello C, Cordero A, Duffy J J Clin Invest. 2023; 133(24).

PMID: 37847564 PMC: 10721147. DOI: 10.1172/JCI161142.

Oncogenic MORC2 in cancer development and beyond.

Zhang S, Guo A, Wang H, Liu J, Dong C, Ren J Genes Dis. 2023; 11(2):861-873.

PMID: 37692502 PMC: 10491978. DOI: 10.1016/j.gendis.2023.05.010.

Clinical Diagnostic and Prognostic Potential of and in Hepatocellular Carcinoma Patients.

Xu S, Gao R, Zhou Y, Yang Y, Zhang Y, Li Q Front Oncol. 2022; 12:862216.

PMID: 35795037 PMC: 9252526. DOI: 10.3389/fonc.2022.862216.

Claudin-2 promotes colorectal cancer growth and metastasis by suppressing NDRG1 transcription.

Wei M, Zhang Y, Yang X, Ma P, Li Y, Wu Y Clin Transl Med. 2021; 11(12):e667.

PMID: 34965023 PMC: 8715829. DOI: 10.1002/ctm2.667.

MiR-188-3p and miR-133b Suppress Cell Proliferation in Human Hepatocellular Carcinoma via Post-Transcriptional Suppression of NDRG1.

Luo Z, Fan Y, Liu X, Liu S, Kong X, Ding Z Technol Cancer Res Treat. 2021; 20:15330338211033074.

PMID: 34355586 PMC: 8358491. DOI: 10.1177/15330338211033074.

References

Yan X, Chua M, Sun H, So S . N-Myc down-regulated gene 1 mediates proliferation, invasion, and apoptosis of hepatocellular carcinoma cells. Cancer Lett. 2008; 262(1):133-42. DOI: 10.1016/j.canlet.2007.12.010. View

Maruyama Y, Ono M, Kawahara A, Yokoyama T, Basaki Y, Kage M . Tumor growth suppression in pancreatic cancer by a putative metastasis suppressor gene Cap43/NDRG1/Drg-1 through modulation of angiogenesis. Cancer Res. 2006; 66(12):6233-42. DOI: 10.1158/0008-5472.CAN-06-0183. View

Cheng J, Xie H, Xu X, Wu J, Wei X, Su R . NDRG1 as a biomarker for metastasis, recurrence and of poor prognosis in hepatocellular carcinoma. Cancer Lett. 2011; 310(1):35-45. DOI: 10.1016/j.canlet.2011.06.001. View

Danielsen S, Lind G, Bjornslett M, Meling G, Rognum T, Heim S . Novel mutations of the suppressor gene PTEN in colorectal carcinomas stratified by microsatellite instability- and TP53 mutation- status. Hum Mutat. 2008; 29(11):E252-62. DOI: 10.1002/humu.20860. View

Siegel R, Naishadham D, Jemal A . Cancer statistics, 2012. CA Cancer J Clin. 2012; 62(1):10-29. DOI: 10.3322/caac.20138. View

Liang J, Gao P, Wang Z, Song Y, Xu Y, Wang M . The integration of macroscopic tumor invasion of adjacent organs into TNM staging system for colorectal cancer. PLoS One. 2013; 7(12):e52269. PMC: 3530549. DOI: 10.1371/journal.pone.0052269. View

Nagai M, Gerhard R, Fregnani J, Nonogaki S, Rierger R, Netto M . Prognostic value of NDRG1 and SPARC protein expression in breast cancer patients. Breast Cancer Res Treat. 2010; 126(1):1-14. DOI: 10.1007/s10549-010-0867-2. View

Ando T, Ishiguro H, Kimura M, Mitsui A, Kurehara H, Sugito N . Decreased expression of NDRG1 is correlated with tumor progression and poor prognosis in patients with esophageal squamous cell carcinoma. Dis Esophagus. 2006; 19(6):454-8. DOI: 10.1111/j.1442-2050.2006.00618.x. View

Chen Z, Zhang D, Yue F, Zheng M, Kovacevic Z, Richardson D . The iron chelators Dp44mT and DFO inhibit TGF-β-induced epithelial-mesenchymal transition via up-regulation of N-Myc downstream-regulated gene 1 (NDRG1). J Biol Chem. 2012; 287(21):17016-17028. PMC: 3366822. DOI: 10.1074/jbc.M112.350470. View

10.

Bolocan A, Ion D, Ciocan D, Paduraru D . Prognostic and predictive factors in colorectal cancer. Chirurgia (Bucur). 2012; 107(5):555-63. View

11.

Le N, Richardson D . Iron chelators with high antiproliferative activity up-regulate the expression of a growth inhibitory and metastasis suppressor gene: a link between iron metabolism and proliferation. Blood. 2004; 104(9):2967-75. DOI: 10.1182/blood-2004-05-1866. View

12.

Tabusa H, Brooks T, Massey A . Knockdown of PAK4 or PAK1 inhibits the proliferation of mutant KRAS colon cancer cells independently of RAF/MEK/ERK and PI3K/AKT signaling. Mol Cancer Res. 2012; 11(2):109-21. DOI: 10.1158/1541-7786.MCR-12-0466. View

13.

Popa F, Bratucu M, Radu P . Present and future tense in operable rectal cancer. Chirurgia (Bucur). 2011; 106(1):11-6. View

14.

Bandyopadhyay S, Pai S, Gross S, Hirota S, Hosobe S, Miura K . The Drg-1 gene suppresses tumor metastasis in prostate cancer. Cancer Res. 2003; 63(8):1731-6. View

15.

Sun J, Zhang D, Zheng Y, Zhao Q, Zheng M, Kovacevic Z . Targeting the metastasis suppressor, NDRG1, using novel iron chelators: regulation of stress fiber-mediated tumor cell migration via modulation of the ROCK1/pMLC2 signaling pathway. Mol Pharmacol. 2012; 83(2):454-69. DOI: 10.1124/mol.112.083097. View

16.

Sidhu R, Rong A, Dahlberg S . Evaluation of progression-free survival as a surrogate endpoint for survival in chemotherapy and targeted agent metastatic colorectal cancer trials. Clin Cancer Res. 2013; 19(5):969-76. DOI: 10.1158/1078-0432.CCR-12-2502. View

17.

Bao B, Ali S, Ahmad A, Azmi A, Li Y, Banerjee S . Hypoxia-induced aggressiveness of pancreatic cancer cells is due to increased expression of VEGF, IL-6 and miR-21, which can be attenuated by CDF treatment. PLoS One. 2012; 7(12):e50165. PMC: 3521759. DOI: 10.1371/journal.pone.0050165. View

18.

Fujii T, Yokoyama G, Takahashi H, Namoto R, Nakagawa S, Toh U . Preclinical studies of molecular-targeting diagnostic and therapeutic strategies against breast cancer. Breast Cancer. 2008; 15(1):73-8. DOI: 10.1007/s12282-007-0015-y. View

19.

Zhang D, Tai L, Wong L, Chiu L, Sethi S, Koay E . Proteomic study reveals that proteins involved in metabolic and detoxification pathways are highly expressed in HER-2/neu-positive breast cancer. Mol Cell Proteomics. 2005; 4(11):1686-96. DOI: 10.1074/mcp.M400221-MCP200. View

20.

Li Q, Chen H . Transcriptional silencing of N-Myc downstream-regulated gene 1 (NDRG1) in metastatic colon cancer cell line SW620. Clin Exp Metastasis. 2010; 28(2):127-35. DOI: 10.1007/s10585-010-9366-4. View