14-3-3sigma expression as a prognostic marker in undifferentiated nasopharyngeal carcinoma.
In this study, we investigated the expression of 14-3-3sigma tumor suppressor gene in a panel of NPC cell lines, xenografts and primary tumors. Our objective was to determine the correlation between 14-3-3sigma expression and clinical outcome in NPC. We detected reduced 14-3-3sigma expression in 5/6 NPC tumor lines by quantitative RT-PCR and Western blotting. By immunohistochemical staining, significant down-regulation of 14-3-3sigma was also found in 26/72 (36.1%) primary tumors of NPC patients, who were treated with curative radiotherapy. Promoter methylation was confirmed in a subset of primary tumors by methylation-specific PCR analysis. Importantly, we demonstrated that 14-3-3sigma expression is significantly associated with both overall survival (OS) and cancer-specific survival (CSS), but not with the clinical staging of NPC patients. The low 14-3-3sigma expression was associated with improved overall (p=0.029) and cancer-specific survival (p=0.042) on univariate analysis. 14-3-3sigma expression and staging were also independent variables to all the prognostic factors under multivariate analysis. In conclusion, low expression of 14-3-3sigma appears to be a valuable marker for better survival in patient with NPC. These results provide the evidence that 14-3-3sigma expression is a significant prognostic factor for NPC patients.
Chan
Sylvia Yat-Yee
SY
Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, SAR, P.R. China.
To
Ka-Fai
KF
Leung
Sing-Fai
SF
Yip
William Wai-Lun
WW
Mak
Michael Ko-Fung
MK
Chung
Grace Tin-Yun
GT
Lo
Kwok-Wai
KW
D048948:14-3-3 Proteins / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000096:biosynthesis; D015153:Blotting, Western; D002277:Carcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D019175:DNA Methylation; D005092:Exonucleases / Q000096:biosynthesis*; D005095:Exoribonucleases; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human