DDX3 as a strongest prognosis marker and its downregulation promotes metastasis in colorectal cancer
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Chia-Yi Su1,*, Tsung-Chieh Lin1,*, Yuan-Feng Lin2, Ming-Huang Chen3, Chien-Hsin Lee1, Hsuan-Yao Wang4, Yu-Chieh Lee5, Yu-Peng Liu6, Chi-Long Chen7,8 and Michael Hsiao1
1 Genomics Research Center, Academia Sinica, Taipei, Taiwan
2 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
3 Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
4 Graduate Program of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los Angeles, USA
5 Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan
6 Department of Genome Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
7 Department of Pathology, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
8 Department of Pathology, College of Medicine, Taipei Medical University, Taipei, Taiwan
* These authors have contributed equally to this work
Michael Hsiao, email:
Chi-Long Chen, email:
Keywords: DDX3, colorectal cancer, prognosis, metastasis, E-cadherin
Received: December 12, 2014 Accepted: May 12, 2015 Published: June 02, 2015
Background: Conflicting results regarding the role of DEAD-box polypeptide 3 (DDX3) are seen not only between cancer types but also within the same type of cancer. In this study, we aimed at clarifying the prognostic significance of DDX3 in patients of major cancer types through large cohort survival analysis and further investigated its effects on cancer progression.
Methods: Large cohort survival analysis of 7 cancer types, including colorectal cancer, breast cancer, lung cancer, head and neck cancer, liver cancer, glioblastoma, and ovarian cancer, was performed using public database at RNA level and was further confirmed by IHC analysis at protein level. Phenotype parameters of DDX3 knockdown colon cancer cells and the mechanism of DDX3 regulated cancer progression were investigated in vitro and in vivo.
Results: In large cohort survival analysis, DDX3 had a significant prognostic predictive power in colorectal cancer at both RNA and protein level. Patients with low DDX3 expression had poor prognosis and frequent distant metastasis. Knockdown of DDX3 enhanced the migration and invasion abilities of colon cancer cells and promoted tumor metastasis in vivo. Snail upregulation with decreased membranous E-cadherin expression and reduced cell aggregation were found after DDX3 downregulation.
Conclusions: Our study revealed the strong prognostic effect of DDX3 on colorectal cancer among seven major cancer types through larger cohort survival analysis at RNA and protein level. Low DDX3 expression promotes Snail/E-cadherin pathway mediated cancer metastasis and poor clinical outcome in colorectal cancer patients.
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