Forkhead box O-class 1 and forkhead box G1 as prognostic markers for bladder cancer.
Forkhead box O-class 1 (FOXO1) is a key regulator of glucose homeostasis, cell-cycle progression, and apoptosis. Its functions are modulated by forkhead box G1 (FOXG1), which acts as a transcriptional repressor with oncogenic potential. Real-time PCR and immunohistochemical staining were performed in 174 primary bladder cancer specimens and 21 normal bladder mucosae to evaluate these genes. FOXO1 and FOXG1 mRNA expression in cancer tissues were higher than in normal mucosae (each P<0.001). FOXO1 mRNA levels were significantly higher in samples of non-progressed patients (P<0.001), but FOXG1 were enhanced in those of progressed patients (P=0.019). On univariate analysis, FOXO1 mRNA expression was significantly associated with grade, stage, recurrence, progression and survival (each P<0.05). On multivariate analysis, increased FOXO1 mRNA expression was associated with both reduced disease progression (odds ratio [OR], 0.367; 95% confidence interval [CI], 0.163-0.826, P=0.015) and enhanced disease-free survival (OR, 3.262; 95% CI, 1.361-7.820, P=0.008). At a median follow-up of 33 months (range 2 to 156), the patients with a high FOXO1 mRNA expression had a significantly prolonged survival (P=0.001). Immunohistochemical findings of FOXO1 were generally concordant with mRNA expression levels. In conclusion, FOXO1 may be a promising marker for predicting progression in human bladder cancers.
Kim
Tae-Hwan
TH
Department of Urology, School of Medicine, Kyung Hee University, Seoul, Korea.
Jo
Sung-Whan
SW
Lee
Young Suk
YS
Kim
Yong-June
YJ
Lee
Sang-Cheol
SC
Kim
Wun-Jae
WJ
Yun
Seok Joong
SJ
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000032:analysis* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000235:genetics; D016017:Odds Ratio; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D012372:ROC Curve; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology*
D014408:Biomarkers, Tumor; C090173:FOXG1 protein, human; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger