Prognostic significance of Jab1 expression in laryngeal squamous cell carcinomas.
OBJECTIVE
Jun activation domain-binding protein 1 (Jab1) is known as a coactivator of AP1 transcription factor, which contributes to tumor progression by degrading the p27kip1 protein. The purpose of this study is to investigate whether Jab1 expression is correlated with p27kip1 level and cell proliferation, as well as whether Jab1 expression is associated with clinicopathologic variables and prognosis of laryngeal squamous cell carcinoma (LSCC).


METHODS
Immunohistochemical and/or Western blot analysis was done in HEp-2 cells and 102 cases of LSCCs.


RESULTS
Jab1 expression was negatively associated with p27kip1 expression and was positively associated with cell proliferation both in HEp-2 cells and LSCCs. Jab1 overexpression was detected in 51% LSCCs and was significantly associated with unfavorable clinicopathologic variables. Survival analysis revealed that Jab1 overexpression is significantly associated with short disease-free and overall survival (P = 0.0036 and P = 0.0001, respectively). When Jab1 and p27kip1 are combined, patients with Jab1(+)/p27kip1(-) revealed poor disease-free and overall survival (P= 0.0008 and P < 0.0001, respectively). When Jab1 expression and lymph node status are combined, patients with Jab1(+)/lymph node(+) revealed poorer disease-free andoverall survival than others (P < 0.0001 and P < 0.0001, respectively). Furthermore, patients with the phenotype of Jab1(+)/p27kip1(-)/lymph node(+) revealed the worst disease-free and overall survival (P < 0.0001 and P < 0.0001, respectively). Multivariate analysis revealed that Jab1 protein is an independent prognostic indicator for overall survival.


CONCLUSIONS
These findings suggested that Jab1 protein may contribute to the tumor progression and represent a novel prognostic indicator for LSCCs.
Dong
Youyi
Y
Department of Cell Physiology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Sui
Li
L
Watanabe
Yasuo
Y
Yamaguchi
Fuminori
F
Hatano
Naoya
N
Tokuda
Masaaki
M
D000328:Adult; D000818:Animals; D015153:Blotting, Western; D000075686:COP9 Signalosome Complex; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality*; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D007822:Laryngeal Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality*; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D015233:Models, Statistical; D015999:Multivariate Analysis; D041681:NIH 3T3 Cells; D010447:Peptide Hydrolases / Q000096:biosynthesis*; D010641:Phenotype; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis*; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; C501490:Cops5 protein, mouse; D000075686:COP9 Signalosome Complex