TY - JOUR
T1 - Akt activation correlates with snail expression and potentially determines the recurrence of prostate cancer in patients at stage T2 after a radical prostatectomy
AU - Chen, Wei Yu
AU - Hua, Kuo Tai
AU - Lee, Wei Jiunn
AU - Lin, Yung Wei
AU - Liu, Yen Nien
AU - Chen, Chi Long
AU - Wen, Yu-Ching
AU - Chien, Ming Hsien
N1 - Publisher Copyright:
© 2016 by the authors; licensee MDPI, Basel, Switzerland.
PY - 2016/8
Y1 - 2016/8
N2 - Our previous work demonstrated the epithelial-mesenchymal transition factor, Snail, is a potential marker for predicting the recurrence of localized prostate cancer (PCa). Akt activation is important for Snail stabilization and transcription in PCa. The purpose of this study was to retrospectively investigate the relationship between the phosphorylated level of Akt (p-Akt) in radical prostatectomy (RP) specimens and cancer biochemical recurrence (BCR). Using a tissue microarray and immunohistochemistry, the expression of p-Akt was measured in benign and neoplastic tissues from RP specimens in 53 patients whose cancer was pathologically defined as T2 without positive margins. Herein, we observed that the p-Akt level was higher in PCa than in benign tissues and was significantly associated with the Snail level. A high p-Akt image score (≥8) was significantly correlated with a higher histological Gleason sum, Snail image score, and preoperative prostate-specific antigen (PSA) value. Moreover, the high p-Akt image score and Gleason score sum (≥7) showed similar discriminatory abilities for BCR according to a receiver-operator characteristic curve analysis and were correlated with worse recurrence-free survival according to a log-rank test (p < 0.05). To further determine whether a high p-Akt image score could predict the risk of BCR, a Cox proportional hazard model showed that only a high p-Akt image score (hazard ratio (HR): 3.12, p=0.05)and a high Gleason score sum (≥7)(HR:1.18,p=0.05)butnotahighpreoperativePSA value (HR: 0.62, p = 0.57) were significantly associated with a higher risk of developing BCR. Our data indicate that, for localized PCa patients after an RP, p-Akt can serve as a potential prognostic marker that improves predictions of BCR-free survival.
AB - Our previous work demonstrated the epithelial-mesenchymal transition factor, Snail, is a potential marker for predicting the recurrence of localized prostate cancer (PCa). Akt activation is important for Snail stabilization and transcription in PCa. The purpose of this study was to retrospectively investigate the relationship between the phosphorylated level of Akt (p-Akt) in radical prostatectomy (RP) specimens and cancer biochemical recurrence (BCR). Using a tissue microarray and immunohistochemistry, the expression of p-Akt was measured in benign and neoplastic tissues from RP specimens in 53 patients whose cancer was pathologically defined as T2 without positive margins. Herein, we observed that the p-Akt level was higher in PCa than in benign tissues and was significantly associated with the Snail level. A high p-Akt image score (≥8) was significantly correlated with a higher histological Gleason sum, Snail image score, and preoperative prostate-specific antigen (PSA) value. Moreover, the high p-Akt image score and Gleason score sum (≥7) showed similar discriminatory abilities for BCR according to a receiver-operator characteristic curve analysis and were correlated with worse recurrence-free survival according to a log-rank test (p < 0.05). To further determine whether a high p-Akt image score could predict the risk of BCR, a Cox proportional hazard model showed that only a high p-Akt image score (hazard ratio (HR): 3.12, p=0.05)and a high Gleason score sum (≥7)(HR:1.18,p=0.05)butnotahighpreoperativePSA value (HR: 0.62, p = 0.57) were significantly associated with a higher risk of developing BCR. Our data indicate that, for localized PCa patients after an RP, p-Akt can serve as a potential prognostic marker that improves predictions of BCR-free survival.
KW - Akt
KW - Biochemical recurrence
KW - Prostate cancer
KW - Radical prostatectomy
KW - Snail
KW - Stage T2
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UR - https://www.scopus.com/results/citedbyresults.uri?sort=plf-f&cite=2-s2.0-85015600598&src=s&imp=t&sid=532929666fb8221f866a5105dc77fb5d&sot=cite&sdt=a&sl=0&origin=recordpage&editSaveSearch=&txGid=0cbb194af6e82207b12d63ec303155b7
U2 - 10.3390/ijms17081194
DO - 10.3390/ijms17081194
M3 - Article
C2 - 27455254
AN - SCOPUS:85015600598
SN - 1661-6596
VL - 17
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 8
M1 - 1194
ER -