Overexpression of Jun activation domain-binding protein 1 in nonsmall cell lung cancer and its significance in p27 expression and clinical features.
BACKGROUND
Decreased expression of p27, which is an inhibitor of cyclin-dependent kinase, is associated with cancer aggressiveness. It is believed that Jun activation domain-binding protein 1 (Jab1) plays a role in p27 degradation in a manner that is independent from the role played by S-phase kinase-associated protein 2 (Skp2). To examine the clinical significance of Jab1 in nonsmall cell lung cancer (NSCLC), the protein expression of Jab1 in tumor tissues was investigated with regard to the expression of p27 and Skp2.


METHODS
The clinicopathologic features and immunohistochemical expression levels of Jab1, p27, and Skp2 proteins were studied in 138 specimens from patients who underwent surgical resection for NSCLC. Survival analyses were performed by using the Kaplan-Meier method and Cox regression models.


RESULTS
High Jab1 expression (>50% of cancer cell nuclei stained) was observed in 81 specimens (59%). In Skp2-negative specimens (n = 81), an inverse correlation between the protein expression of p27 and Jab1 was observed both with the chi-square test (P = .02) and with the Mann-Whitney U test (P = .02). High Jab1 expression levels were related to poor outcomes in 118 patients who underwent complete resection, with a 5-year overall survival rate of 43.9% for patients who had high Jab1 expression and 63.1% for patients who had low Jab1 expression (P = .01). This difference was greater in patients who had Skp2-negative specimens (51.9% vs. 79.3% (P = .02), but it was not significant in patients who had Skp2-positive specimens. The multivariate analysis revealed that Jab1 expression was an independent prognostic factor for survival in patients with NSCLC (relative risk, 2.247; P = .01).


CONCLUSIONS
The current results showed for the first time that high Jab1 protein expression is related to poor outcome in patients with NSCLC and that this protein may be a target of therapy in NSCLC.
Osoegawa
Atsushi
A
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. osoegawa-ths@umin.ac.jp
Yoshino
Ichiro
I
Kometani
Takuro
T
Yamaguchi
Masafumi
M
Kameyama
Toshifumi
T
Yohena
Tomofumi
T
Maehara
Yoshihiko
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D000075686:COP9 Signalosome Complex; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D007564:Japan; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000096:biosynthesis*; D011237:Predictive Value of Tests; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis*; D044786:S-Phase Kinase-Associated Proteins / Q000096:biosynthesis; D016019:Survival Analysis; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; D018809:Proliferating Cell Nuclear Antigen; D044786:S-Phase Kinase-Associated Proteins; C413374:p27 antigen; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex