title: DDX3X Biomarker Correlates with Poor Survival in Human Gliomas.
abstract: Primary high-grade gliomas possess invasive growth and lead to unfavorable survival outcome. The investigation of biomarkers for prediction of survival outcome in patients with gliomas is important for clinical assessment. The DEAD (Asp-Glu-Ala-Asp) box helicase 3, X-linked (DDX3X) controls tumor migration, proliferation, and progression. However, the role of DDX3X in defining the pathological grading and survival outcome in patients with human gliomas is not yet clarified. We analyzed the DDX3X gene expression, WHO pathological grading, and overall survival from de-linked data. Further validation was done using quantitative RT-PCR of cDNA from normal brain and glioma, and immunohistochemical (IHC) staining of tissue microarray. Statistical analysis of GEO datasets showed that DDX3X mRNA expression demonstrated statistically higher in WHO grade IV (n = 81) than in non-tumor controls (n = 23, p = 1.13 × 10(-10)). Moreover, DDX3X level was also higher in WHO grade III (n = 19) than in non-tumor controls (p = 2.43 × 10(-5)). Kaplan-Meier survival analysis showed poor survival in patients with high DDX3X mRNA levels (n = 24) than in those with low DDX3X expression (n = 53) (median survival, 115 vs. 58 weeks, p = 0.0009, by log-rank test, hazard ratio: 0.3507, 95% CI: 0.1893-0.6496). Furthermore, DDX3X mRNA expression and protein production significantly increased in glioma cells compared with normal brain tissue examined by quantitative RT-PCR, and Western blot. IHC staining showed highly staining of high-grade glioma in comparison with normal brain tissue. Taken together, DDX3X expression level positively correlates with WHO pathologic grading and poor survival outcome, indicating that DDX3X is a valuable biomarker in human gliomas.
authors.affiliation: Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Taipei 11490, Taiwan. hondy2195@yahoo.com.tw.|Department of Biochemistry, National Defense Medical Center, No. 325, Section 2, Taipei 11490, Taiwan. hondy2195@yahoo.com.tw.
authors.forename: Dueng-Yuan
authors.initials: DY
authors.lastname: Hueng
authors.affiliation: Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan. drtsaiwenchuan@mail2000.com.tw.
authors.forename: Wen-Chiuan
authors.initials: WC
authors.lastname: Tsai
authors.affiliation: Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Taipei 11490, Taiwan. phoenixchiou@gmail.com.
authors.forename: Hsin-Ying Clair
authors.initials: HY
authors.lastname: Chiou
authors.affiliation: Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Taipei 11490, Taiwan. heisenber0930@gmail.com.
authors.forename: Shao-Wei
authors.initials: SW
authors.lastname: Feng
authors.affiliation: Graduate Institute of Life Science, National Defense Medical Center, Taipei 11490, Taiwan. xup6fup@hotmail.com.
authors.forename: Chin
authors.initials: C
authors.lastname: Lin
authors.affiliation: Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan. liyaofeng1109@gmail.com.
authors.forename: Yao-Feng
authors.initials: YF
authors.lastname: Li
authors.affiliation: Department of Biochemistry, National Defense Medical Center, No. 325, Section 2, Taipei 11490, Taiwan. emily7781@hotmail.com.
authors.forename: Li-Chun
authors.initials: LC
authors.lastname: Huang
authors.affiliation: Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei 11490, Taiwan. blimp1@hotmail.com.tw.
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Lin
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005910:Glioma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D060066:Protein Interaction Maps; D012333:RNA, Messenger; D060888:Real-Time Polymerase Chain Reaction; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C119332:DDX3X protein, human; D053487:DEAD-box RNA Helicases
keywords: DDX3X; GEO profile; RNA Helicase DDX3X; WHO grades; glioma; tissue microarray