title: Y-Box-binding protein-1 is a promising predictive marker of radioresistance and chemoradioresistance in nasopharyngeal cancer.
abstract: The Y-Box-binding protein-1, a member of the cold-shock domain DNA- and RNA-binding protein superfamily, is known to mediate chemoresistance. The aim of this study was to determine the expression of Y-Box-binding protein-1 in nasopharyngeal cancer in vitro and in tumor tissue samples as well as analyze the clinicopathological significance of Y-Box-binding protein-1 expression in nasopharyngeal cancer, in particular as a predictor of outcome after treatment. The Y-Box-binding protein-1 expression profile was evaluated at the mRNA and protein levels in poorly differentiated CNE-2 nasopharyngeal cancer cells by real-time RT-PCR, western blot analysis and immunohistochemistry. Y-Box-binding protein-1 expression in 143 nasopharyngeal cancer specimens was examined by immunohistochemistry and correlated with clinicopathologic parameters. Y-Box-binding protein-1 mRNA and protein were found to be expressed in CNE-2 nasopharyngeal cancer cells in vitro. Of 143 patient tissue sections, 137 (96%) were stained positive for the Y-Box-binding protein-1 protein. Y-Box-binding protein-1 immunostaining was observed to be predominantly cytoplasmic. A higher recurrence of nasopharyngeal cancer was found in patients whose tissues had increased Y-Box-binding protein-1 expression (P<0.001). The Cox proportionate hazard regression model also established that high Y-Box-binding protein-1 immunoreactivity was significantly correlated with increased risk (2.13 times) of recurrence as compared to low Y-Box-binding protein-1 immunoreactivity (P=0.01). Within groups of patients treated by radiotherapy or chemoradiotherapy, recurrent cases had significantly higher Y-Box-binding protein-1 expression than nonrecurrent cases (P<0.001 and P=0.0035, respectively). These data suggest that Y-Box-binding protein-1 expression has clinicopathological significance with potential as a predictive marker of recurrence in nasopharyngeal cancer patients who undergo radiotherapy or chemoradiotherapy.
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Wei-Lin
authors.initials: WL
authors.lastname: Tay
authors.forename: George Wai-Cheong
authors.initials: GW
authors.lastname: Yip
authors.forename: Puay-Hoon
authors.initials: PH
authors.lastname: Tan
authors.forename: Ken
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Richard
authors.initials: R
authors.lastname: Yeo
authors.forename: Tze-Pin
authors.initials: TP
authors.lastname: Ng
authors.forename: Srinivasan Dinesh
authors.initials: SD
authors.lastname: Kumar
authors.forename: Masafumi
authors.initials: M
authors.lastname: Tsujimoto
authors.forename: Boon-Huat
authors.initials: BH
authors.lastname: Bay
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001706:Biopsy; D015153:Blotting, Western; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000235:genetics / Q000532:radiotherapy; D009687:Nuclear Proteins / Q000032:analysis* / Q000235:genetics; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000032:analysis; D018714:Radiotherapy, Adjuvant; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D017211:Treatment Failure; D051840:Y-Box-Binding Protein 1; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human