Chuan Liu1, Xiaowei Fu2, Zhiwei Zhong2, Jing Zhang3, Haiyan Mou1, Qiong Wu3, Tianle Sheng1, Bo Huang4, Yeqing Zou5. 1. Jiangxi Province Key Laboratory of Molecular Medicine, The Second Affiliated Hospital of Nanchang University, No. 1 Min De Road, Nanchang, 330006, China. 2. Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Nanchang University, No. 1 Min De Road, Nanchang, 330006, China. 3. Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang University, No. 1 Min De Road, Nanchang, 330006, China. 4. Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang University, No. 1 Min De Road, Nanchang, 330006, China. huangbo6112@163.com. 5. Jiangxi Province Key Laboratory of Molecular Medicine, The Second Affiliated Hospital of Nanchang University, No. 1 Min De Road, Nanchang, 330006, China. zouyeqing3366@163.com.
Abstract
BACKGROUND: The chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) plays a key role in controlling various cellular phenomena, including immune-mediated inflammation, transformation, apoptosis, cell cycle progression, and proliferation. METHODS: This study investigated the function and clinical significance of CHD1L protein expression in pancreatic cancer (PC). We analyzed CHD1L expression in surgical specimens from 112 PC patients. The correlation between the clinical characteristics and prognosis was also determined. Futhermore, cell proliferation were measured using EDU, and a molecular mechanism of Wnt/β-catenin pathway regulation by CHD1L was explored. RESULT: CHD1L protein expression was significantly higher in PC patients with regard to the tumor grade, stage, size, differentiation and lymph node status. Increased CHD1L protein expression was significantly associated with poor overall survival. Multivariate analyses revealed that high CHD1L expression was an independent predictive marker for the recurrence and poor prognosis of pancreatic cancer. Furthermore, silencing of CHD1L expression by RNAi effectively abolished the proliferative abilities of CHD1L in vivo and in vitro. We found that the Wnt/β-catenin pathway contributed to the effect of CHD1L-mediated pancreatic cancer proliferation. CONCLUSION: Taken together, our data provide a novel evidence for the biological and clinical significance of CHD1L as a potential biomarker, and we demonstrate that CHD1L-Wnt/β-catenin might be a novel pathway involved in pancreatic cancer progression.
BACKGROUND: The chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) plays a key role in controlling various cellular phenomena, including immune-mediated inflammation, transformation, apoptosis, cell cycle progression, and proliferation. METHODS: This study investigated the function and clinical significance of CHD1L protein expression in pancreatic cancer (PC). We analyzed CHD1L expression in surgical specimens from 112 PC patients. The correlation between the clinical characteristics and prognosis was also determined. Futhermore, cell proliferation were measured using EDU, and a molecular mechanism of Wnt/β-catenin pathway regulation by CHD1L was explored. RESULT: CHD1L protein expression was significantly higher in PC patients with regard to the tumor grade, stage, size, differentiation and lymph node status. Increased CHD1L protein expression was significantly associated with poor overall survival. Multivariate analyses revealed that high CHD1L expression was an independent predictive marker for the recurrence and poor prognosis of pancreatic cancer. Furthermore, silencing of CHD1L expression by RNAi effectively abolished the proliferative abilities of CHD1L in vivo and in vitro. We found that the Wnt/β-catenin pathway contributed to the effect of CHD1L-mediated pancreatic cancer proliferation. CONCLUSION: Taken together, our data provide a novel evidence for the biological and clinical significance of CHD1L as a potential biomarker, and we demonstrate that CHD1L-Wnt/β-catenin might be a novel pathway involved in pancreatic cancer progression.
Authors: Walid L Shaib; Andrew Ip; Kenneth Cardona; Olatunji B Alese; Shishir K Maithel; David Kooby; Jerome Landry; Bassel F El-Rayes Journal: Oncologist Date: 2016-02-01