title: DDX3 as a strongest prognosis marker and its downregulation promotes metastasis in colorectal cancer.
abstract: 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.
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Chia-Yi
authors.initials: CY
authors.lastname: Su
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Tsung-Chieh
authors.initials: TC
authors.lastname: Lin
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yuan-Feng
authors.initials: YF
authors.lastname: Lin
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Ming-Huang
authors.initials: MH
authors.lastname: Chen
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Chien-Hsin
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Graduate Program of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los Angeles, USA.
authors.forename: Hsuan-Yao
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yu-Chieh
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Department of Genome Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yu-Peng
authors.initials: YP
authors.lastname: Liu
authors.affiliation: Department of Pathology, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.|Department of Pathology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chi-Long
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Michael
authors.initials: M
authors.lastname: Hsiao
mesh_terms: D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism; D030541:Databases, Genetic; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D008875:Middle Aged; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; C119332:DDX3X protein, human; D053487:DEAD-box RNA Helicases
keywords: DDX3; E-cadherin; colorectal cancer; metastasis; prognosis