NDRG4 stratifies the prognostic value of body mass index in colorectal cancer

// Jianyong Zheng 1 , Yunming Li 2 , Shaojun Zhu 3 , Jipeng Li 1 , Qingchuan Zhao 1 , Gang Ji 1 , Weizhong Wang 1 , Dake Chu 1, 4 1 State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an, China 2 Department of Health Statistics, Fourth Military Medical University. Xi’an, China 3 Department of Pathology, Fourth Military Medical University. Xi’an, China 4 Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi’an, China Correspondence to: Dake Chu, e-mail: chudake@hotmail.com Keywords: NDRG4, colorectal cancer, obesity, disease-free survival, overall survival Received: May 12, 2015 Accepted: October 04, 2015 Published: October 20, 2015 ABSTRACT NDRG4 is a novel candidate tumor suppressor and can inhibit PI3K/AKT signal which is related with energy balance and related carcinogenesis. In the present study, we investigated whether NDRG4 status could modify the association of obesity with clinical outcome of colorectal cancer. For this purpose, a hospital-based prospective study cohort of 226 colorectal cancer patients was involved. NDRG4 mRNA levels were determined by real-time PCR. Association of NDRG4 mRNA expression with disease-free and overall survival was studied first. Then, the association of obesity with clinical outcome was determined according to NDRG4 level. Multivariate Cox proportional hazards model was used to compute hazard ratio, adjusting for covariates including microsatellite instability, KRAS, BRAF and PIK3CA mutation. Results showed that NDRG4 mRNA expression was decreased in tumor specimens and significantly correlated with tumor differentiation, invasion and metastasis. Patients with tumor of reduced NDRG4 mRNA level had unfavorable disease-free and overall survival. Obesity was found to be adversely associated with disease-free and overall survival in tumors with reduced NDRG4 level, not in preserved NDRG4 level group, in both univariate and multivariate analysis. These data provided the first evidence that NDRG4 level in colorectal cancer could effectively stratify the prognostic value of obesity, which would better the understanding of the prognostic role of obesity in colorectal cancer. Our results also support the notion that the host-tumor interactions in colorectal cancer might influence tumor aggressiveness.