J Korean Med Sci.  2009 Jun;24(3):468-473. 10.3346/jkms.2009.24.3.468.

Forkhead box O-class 1 and Forkhead box G1 as Prognostic Markers for Bladder Cancer

• Kim TH
• Jo SW
• Lee YS
• Kim YJ
• Lee SC
• Kim WJ
• Yun SJ

• KMID: 1779165
• DOI: http://doi.org/10.3346/jkms.2009.24.3.468

Abstract

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.

Keyword

FOXO1; FOXG1; Urinary Bladder Neoplasms; Prognostic Factor; Real Time PCR; Immunohistochemistry

MeSH Terms

Aged
Disease-Free Survival
Female
Forkhead Transcription Factors/*analysis/genetics
Humans
Male
Middle Aged
Neoplasm Staging
Nerve Tissue Proteins/*analysis/genetics
Odds Ratio
Prognosis
RNA, Messenger/metabolism
ROC Curve
Tumor Markers, Biological/*analysis
Urinary Bladder Neoplasms/metabolism/*pathology

Figure

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  Fig. 1 Disease-free survival and FOXO1 mRNA expression levels. The cut-off point (51.48×103 copies/µL) with the highest combined sensitivity and specificity was determined on ROC curve.

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  Fig. 2 The FOXO1 expression shows strong cytoplasmic reactivity on urothelial cancer cells (×200).

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