Akt Activation Correlates with Snail Expression and Potentially Determines the Recurrence of Prostate Cancer in Patients at Stage T2 after a Radical Prostatectomy

Abstract

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) but not a high preoperative PSA 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.

Advances in Biomarkers for PCa Diagnostics and Prognostics—A Way towards Personalized Medicine

“…In the first accepted paper of this Special issue by Chen et al [ 31 ] the authors used tissue microarray and immunohistochemistry to estimate the phosphorylated levels of Akt (p-Akt) in 53 radical prostatectomy (RP) specimen. Within a Cox proportional hazard model a high p-Akt image score better predicted (hazard ratio (HR): 3.12) the risk of BCR than a high Gleason score (HR: 1.18) or a high PSA (HR: 0.62, p = 0.57) [ 31 ]. It should be noted that the initial 76 RP specimen (23 had to be excluded) were collected over a relatively long time from 1999 to 2011 [ 31 ].…”

“…Within a Cox proportional hazard model a high p-Akt image score better predicted (hazard ratio (HR): 3.12) the risk of BCR than a high Gleason score (HR: 1.18) or a high PSA (HR: 0.62, p = 0.57) [ 31 ]. It should be noted that the initial 76 RP specimen (23 had to be excluded) were collected over a relatively long time from 1999 to 2011 [ 31 ]. A limitation of this second study from Taiwan was a much higher mean PSA (almost 30 ng/mL) in the group of high p-Akt Scores ≥ 8 as compared with the group with a p-Akt Score ≤ 6, where the mean PSA was only 12 ng/mL.…”

“…Two of the four reviews further summarize biomarkers for PCa diagnostic [ 27 ] or active surveillance [ 28 ] while the other two reviews have special topics like nanoparticles as theranostic vehicles [ 29 ] or PCa stem cells [ 30 ]. Four working groups published results by using immunohistochemistry in prostate, lymph node or bone tissue [ 31 , 32 , 33 , 34 ]. This Special Issue also covered studies on seminal plasma biomarkers [ 35 ], improved PET contrast between osteolytic and osteoblastic bone metastatic lesions with fasting [ 36 ] and the impact of the blood collection tube and storage time on CTC-mRNA (AR-V7) analysis [ 37 ].…”

Chronic Exposure to Environmentally Relevant Concentrations of Microcystin-Leucine Arginine Causes Lung Barrier Damage through PP2A Activity Inhibition and Claudin1 Ubiquitination

“…PP2A has been shown to be associated with cellular tight junctions and can regulate tight junction integrity through the Snail pathway via AKT. 23 MC-LR is a potent inhibitor of PP2A; however, the role and mechanism of PP2A in MC-LR-induced lung injury through pulmonary epithelial cell tight junction disruption remain unclear. In addition, ubiquitination is crucial for regulation of cell junctions.…”

The epithelial–mesenchymal transition regulators Twist, Slug, and Snail are associated with aggressive tumour features and poor outcome in prostate cancer patients

“…Twist, Slug, and Snail are associated with aggressive features and disease progression in several cancers [8,[25][26][27][28][29][30] but are studied to a lesser extent in prostate cancer [31][32][33][34][35][36][37][38][39], where studies presenting end points beyond biochemical recurrence are still unavailable. Here, we evaluated the expression of Twist, Slug, and Snail in different prostatic tissues.…”