NDRG4 stratifies the prognostic value of body mass index in colorectal cancer.
NDRG4 stratifies the prognostic value of body mass index in colorectal cancer.
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NDRG4 对体重指数在结直肠癌中的预后价值进行分层
DOI：
10.18632/oncotarget.6182
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发表时间：
2016-01-12
期刊：
影响因子：
--
通讯作者：
Chu D
中科院分区：
文献类型：
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作者：
Zheng J;Li Y;Zhu S;Li J;Zhao Q;Ji G;Wang W;Chu D
NDRG 4是一种新型的肿瘤抑制因子，可抑制与能量平衡相关的PI 3 K/AKT信号，从而抑制肿瘤的发生。在本研究中，我们调查NDRG 4状态是否可以改变肥胖与结直肠癌临床结果的关系。为此目的，一个基于医院的前瞻性研究队列的226例结直肠癌患者参与。通过实时PCR测定NDRG 4 mRNA水平。首先研究NDRG 4 mRNA表达与无病生存期和总生存期的相关性。然后，根据NDRG 4水平确定肥胖与临床结局的相关性。使用多变量考克斯比例风险模型计算风险比，并调整协变量，包括微卫星不稳定性、KRAS、BRAF和PIK 3 CA突变。结果显示，NDRG 4 mRNA在肿瘤组织中表达降低，且与肿瘤分化程度、侵袭转移密切相关。NDRG 4 mRNA水平降低的肿瘤患者的无病生存率和总生存率均不利。在单变量和多变量分析中，发现肥胖与NDRG 4水平降低的肿瘤的无病生存期和总生存期呈负相关，而与NDRG 4水平保持组无关。这些数据首次证明NDRG 4在结直肠癌中的表达水平可以有效地对肥胖的预后价值进行分层，这将有助于更好地理解肥胖在结直肠癌中的预后作用。我们的研究结果也支持了大肠癌中宿主-肿瘤相互作用可能影响肿瘤侵袭性的观点。
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.