title: 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.
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. 1047@tmu.edu.tw.|Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. 1047@tmu.edu.tw.|Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan. 1047@tmu.edu.tw.
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Chen
authors.affiliation: Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei 100, Taiwan. d94447003@gmail.com.
authors.forename: Kuo-Tai
authors.initials: KT
authors.lastname: Hua
authors.affiliation: Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan. lwj5905@gmail.com.|Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. lwj5905@gmail.com.
authors.forename: Wei-Jiunn
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Department of Urology, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan. highwei168@gmail.com.
authors.forename: Yung-Wei
authors.initials: YW
authors.lastname: Lin
authors.affiliation: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan. liuy@tmu.edu.tw.
authors.forename: Yen-Nien
authors.initials: YN
authors.lastname: Liu
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. chcl0997@yahoo.com.tw.|Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. chcl0997@yahoo.com.tw.
authors.forename: Chi-Long
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. s811007@yahoo.com.tw.|Department of Urology, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan. s811007@yahoo.com.tw.
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Wen
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. mhchien1976@gmail.com.|Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan. mhchien1976@gmail.com.
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Chien
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D009367:Neoplasm Staging; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012189:Retrospective Studies; D000071250:Snail Family Transcription Factors / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; Snail; biochemical recurrence; prostate cancer; radical prostatectomy; stage T2