Constitutive phosphorylation of the FOXO1A transcription factor as a prognostic variable in gastric cancer

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Kim, Ji Hun; Kim, Min Kyu; Lee, Hee Eun; Cho, Sung Jin; Cho, Yu Jin; Lee, Byung Lan; Lee, Hye Seung; Nam, Seon Young; Lee, Jae-Seon; Kim, Woo Ho
Issue Date
Nature Publishing Group
Mod Pathol 2007;20(8):835-842.
ApoptosisCarcinoma/*chemistry/mortality/pathology/therapyCell DifferentiationCell ProliferationForkhead Transcription Factors/*analysisGlutathione S-Transferase pi/analysisImmunohistochemistryKaplan-Meiers EstimateNeoplasm InvasivenessNeoplasm StagingPhosphorylationPrognosisProportional Hazards ModelsProto-Oncogene Proteins c-akt/analysisProto-Oncogene Proteins c-bcl-2/analysisStomach Neoplasms/*chemistry/mortality/pathology/therapySuperoxide Dismutase/analysisTissue Array AnalysisTreatment OutcomeTumor Markers, Biological/*analysisTumor Suppressor Proteins/analysis
Increased phosphorylation of FOXO1A, a FOXO transcription factor, has been implicated in several human cancers; however, it has not been studied in the gastric cancer to date. To determine the status of pFOXO1A expression in human gastric cancers and to determine its relationship with other tumor-associated proteins, we performed immunohistochemical staining on tissue array slides containing 272 human gastric carcinoma specimens. In non-neoplastic gastric mucosa, the expression of pFOXO1A was observed primarily in cells in the proliferative zone and in areas of intestinal metaplasia. In gastric carcinomas, the expression of pFOXO1A was observed in 230 (84.6%) out of 272 cases examined, and was positively correlated with the Ki-67-labeling index (P=0.026). The expression of pFOXO1A was higher in the early stages of pTNM (P<0.001), and was inversely correlated with the intestinal type by Lauren's classification (P=0.001), lymphatic invasion (P=0.017) and lymph node metastasis (P<0.001). Moreover, the expression of pFOXO1A was correlated with a longer patient survival (P=0.004). In addition, the expression of pFOXO1A was correlated with that of pAKT1 (P<0.001), PTEN (P=0.009), CDKN2A (P=0.012), APC (P=0.048), SMAD4 (P<0.001), CD82 (P=0.011), and BCL2 (P=0.011). In conclusion, our results showed that the expression of pFOXO1A is a frequent and early event in gastric tumorigenesis and that there is a significant correlation between pFOXO1A and better prognosis. Thus, our data suggest that the expression of pFOXO1A may serve as a valuable prognostic variable in gastric carcinoma and have significant implications for the development and application of targeted therapy.
0893-3952 (Print)
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College of Medicine/School of Medicine (의과대학/대학원)Pathology (병리학전공)Journal Papers (저널논문_병리학전공)
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