High cytoplasmic FOXO1 and pFOXO1 expression in astrocytomas are associated with worse surgical outcome

• Published in: PloS one 2013-07, Vol.8 (7), p.e69260-e69260
• Main Authors: Chen, Chao, Xu, Tao, Zhou, Jinxu, Yan, Yong, Li, Weiqing, Yu, Hongyu, Hu, Guohan, Ding, Xuehua, Chen, Juxiang, Lu, Yicheng
• Format: Article
• Language: English
• Subjects: Adult; Aged; Analysis; Apoptosis; Astrocytoma; Astrocytoma - diagnosis; Astrocytoma - metabolism; Astrocytoma - mortality; Astrocytoma - surgery; Astrocytomas; Autophagy; Biology; Brain; Brain - metabolism; Brain cancer; Brain Neoplasms - diagnosis; Brain Neoplasms - metabolism; Brain Neoplasms - mortality; Brain Neoplasms - surgery; Brain tumors; Cancer therapies; Cell cycle; Cell death; Cyclin-dependent kinases; Cytoplasm - metabolism; Data processing; Development and progression; Female; Forkhead Box Protein O1; Forkhead Transcription Factors - metabolism; FOXO1 protein; Gastric cancer; Glioblastoma; Glioma; Glioma cells; Hospitals; Humans; Kinases; Male; Medical prognosis; Medicine; Middle Aged; Neoplasm Grading; Neoplasm Staging; Neurosurgery; Pathology; Phosphorylation; Prognosis; Prostate cancer; Protein-tyrosine kinase receptors; Quality; Radiation therapy; Signaling; Stomach cancer; Studies; Surgery; Survival; Transcription factors; Treatment Outcome; Tyrosine
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0069260

FOXO1 is at a convergence point of receptor tyrosine kinase (RTK) signaling, which is one of the three core pathways implicated in glioblastoma. It was recently shown that FOXO1 can effectively induce glioma cell death and inhibit tumor growth through cell cycle arrest and apoptosis. We therefore evaluated FOXO1 and pFOXO1 protein expression in 181 primary astrocytoma samples and 16 normal brain samples. Astrocytoma samples expressed higher cytoplasmic FOXO1 and pFOXO1 than normal brain samples. Nuclear pFOXO1 level was significantly higher than nuclear FOXO1 in astrocytomas. High cytoplasmic FOXO1 expression was associated with older onset age (P = 0.001) and higher WHO grade (P = 0.001). The trend was also observed between cytoplasmic pFOXO1 expression and WHO grade although not significant. Univariate survival analysis showed that both high cytoplasmic FOXO1 and pFOXO1 expression indicated a significantly shorter median overall survival and progression-free survival. Multivariate survival analysis revealed cytoplasmic FOXO1 expression, cytoplasmic pFOXO1 expression, WHO grade, gender, extent of resection and radiotherapy to be independent prognostic factors for overall survival and progression-free survival. Thus, our data suggested that cytoplasmic FOXO1 and pFOXO1 expression may serve as valuable prognostic variables in astrocytomas and may have significant implications for the development and application of targeted therapy.