NDRG4, a novel candidate tumor suppressor, is a predictor of overall survival of colorectal cancer patients

被引:30
作者
Chu, Dake [1 ,2 ,3 ]
Zhang, Zixi [4 ]
Zhou, Yi [5 ]
Li, Yunming [6 ]
Zhu, Shaojun [7 ]
Zhang, Jian [3 ]
Zhao, Qingchuan [1 ,2 ]
Ji, Gang [1 ,2 ]
Wang, Weizhong [1 ,2 ]
Zheng, Jianyong [1 ,2 ]
机构
[1] Fourth Mil Med Univ, Xijing Hosp, State Key Lab Canc Biol, Xian 710032, Peoples R China
[2] Fourth Mil Med Univ, Xijing Hosp, Xijing Hosp Digest Dis, Xian 710032, Peoples R China
[3] Fourth Mil Med Univ, Dept Biochem & Mol Biol, State Key Lab Canc Biol, Xian 710032, Peoples R China
[4] Fourth Mil Med Univ, Xijing Hosp, Dept Plast Surg, Xian 710032, Peoples R China
[5] Tianjin Union Med Ctr, Dept Gastrointestinal Surg, Tianjin, Peoples R China
[6] Chengdu Mil Gen Hosp, Stat Off, Chengdu, Sichuan Provinc, Peoples R China
[7] Fourth Mil Med Univ, Dept Pathol, Xian 710032, Peoples R China
基金
中国博士后科学基金; 国家高技术研究发展计划(863计划); 中国国家自然科学基金;
关键词
NDRG4; PI3K-AKT; colorectal cancer; carcinogenesis; progression; COLON-CANCER; GENE-EXPRESSION; DOWN-REGULATION; MYC; INFLAMMATION; PATHWAY; FAMILY; GLIOBLASTOMA; MUTATION; KRAS;
D O I
10.18632/oncotarget.3170
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The role of NDRG4 in human malignancies is largely unknown. We investigated the role of NDRG4 protein in colorectal cancer and its prognostic value in a hospital-based retrospective training cohort of 272 patients and a prospective validation cohort of 708 patients were. Cell line was transfected with an NDRG4 expression construct to confirm the suppression of PI3K-AKT activity by NDRG4. Appropriate statistical methods were utilized for analysis. Results showed that NDRG4 protein expression was significantly decreased from normal mucosa, chronic colitis, ulcerative colitis, atypical hyperplasia to colorectal cancer. Significant negative correlations were found between NDRG4 staining and p-AKT. Patients with positive NDRG4 staining had favorable survival in both study cohorts. In multivariate analysis, NDRG4 staining proved to be an independent predictor of overall survival. Moreover, the prognostic role of NDRG4 was stratified by p-AKT. Overexpression of NDRG4 in colorectal cancer cell can significantly suppress PI3K-AKT activity, even after EGF stimulation. These results indicated NDRG4 protein expression was decreased in colorectal cancer. It may play its tumor suppressive role in carcinogenesis and progression through attenuation of PI3K-AKT activity. Therefore, high risk colorectal cancer patients could be better identified based on the combination of NDRG4 and PI3K-AKT activity.
引用
收藏
页码:7584 / 7596
页数:13
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