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Histopathological classification of human prostate cancer (PCA) relies on the morphological assessment of tissue specimens but has limited prognostic value. To address this deficiency, we performed comparative transcriptome analysis of human prostatic acini generated in a three-dimensional basement membrane that recapitulates the differentiated morphological characteristics and gene expression profile of a human prostate glandular epithelial tissue. We then applied an acinar morphogenesis-specific gene profile to two independent cohorts of patients with PCA (total n = 79) and found that those with tumors expressing this profile, which we designated acini-like tumors, had a significantly lower risk of postoperative relapse compared with those tumors with a lower correlation (hazard ratio, 0.078; log-rank test P = 0.009). Multivariate analyses showed superior prognostic prediction performance using this classification system compared with clinical criteria and Gleason scores. We prioritized the genes in this profile and identified programmed cell death protein 4 (PDCD4) and Kruppel-like factor 6 (KLF6) as critical regulators and surrogate markers of prostatic tissue architectures, which form a gene signature that robustly predicts clinical prognosis with a remarkable accuracy in several large series of PCA tumors (total n = 161; concordance index, 0.913 to 0.951). Thus, by exploiting the genomic program associated with prostate glandular differentiation, we identified acini-like PCA and related molecular markers that significantly enhance prognostic prediction of human PCA.

Aim: In this study, we administered a questionnaire to consecutive prostate cancer patients who received androgen deprivation therapy (ADT) for understanding the prevalence of depression symptoms.Materials and Methods: We retrospectively identified patients with prostate adenocarcinoma who received ADT between January 2015 and February 2018 at Mackay Memorial Hospital. The patients were then asked to complete the Chinese version of the Patient Health Questionnaire-9 (PHQ-9) during an interview. The patients were divided into two groups according to PHQ-9 score: those with depression symptoms (PHQ-9 ≥ 6, depression group), and those without depression symptoms (PHQ-9 < 6, non-depression group). Two groups were compared using t-tests and correlation coefficients, as appropriate. Statistical significance was set at p < .05.Results: There were no significant correlations between PHQ-9 scores and any of the parameters in the patients overall. In subgroup analysis, a positive correlation was found between the duration of ADT and PHQ-9 score in the patients with depression symptoms (p = .03). In addition, univariate analysis showed a positive association between the duration of ADT and PHQ-9 score, and a longer duration of ADT was further independently associated with increased PHQ-9 score in multivariate analysis in the patients with depression symptoms.Conclusion: This study demonstrated that in patients with prostate cancer and depression symptoms, the severity of the depression symptoms was positively correlated with the duration of ADT. In contrast, this association was not found in patients without depression symptoms. [ABSTRACT FROM AUTHOR]

Introduction. Radiation therapy using ionizing radiation is widely used for the treatment of prostate cancer. The intrinsic radiation sensitivity of cancer cells could be enhanced by modulating multiple factors including the capacity to repair DNA damage, especially double-strand breaks (DSBs). We aimed to examine the effect of zerumbone on radiation sensitivity and its protective effects against ionizing radiation–induced DSB in human prostate cancer cells. Materials and Methods. The human prostate cancer PC3 and DU145 cell lines were used. A colony formation assay was performed to analyze the radiation survival of cells. DNA histogram and generation of reactive oxygen species (ROS) were examined using flow cytometry. Western blotting was used to examine the expression of regulatory molecules related to DNA damage repair. Results. Pretreatment with zerumbone enhanced the radiation effect on prostate cancer cells. Zerumbone delayed the abrogation of radiation-induced expression of γ-H2AX, an indicator of DNA DSB. Zerumbone pretreatment markedly reduced ionizing radiation–induced upregulated expression of phosphorylated ATM (ataxia telangiectasia-mutated), which was partially reversed by the ATM agonist methyl methanesulfonate. Ionizing radiation augmented and zerumbone pretreatment reduced the expression of Jak2 and Stat3, which are involved in DNA damage repair signaling. No significant effect on the generation of ROS and expression of ATR was noted after zerumbone treatment. Conclusion: Zerumbone sensitized DU145 and PC3 prostatic cancer cells to ionizing radiation by modulating radiation-induced ATM activation during repair of DNA DSBs. [ABSTRACT FROM AUTHOR]

Objective To present the transition from laparoscopic radical prostatectomy (LRP) to robotic-assisted laparoscopic radical prostatectomy (RALP) over 10 years in a medium volume center by a single surgeon. Materials and methods We retrospectively reviewed 140 prostate cancer patients who underwent LRP (100 patients) or RALP (40 patients) between May 2005 and May 2015. Preoperative parameters included age, body mass index, and serum prostate specific antigen. Operative course parameters included operative time, estimated blood loss, intraoperative blood transfusion, conversion to open surgery, hospitalization days, duration of Foley catheterization, and complications. Pathological stage, surgical margin status, biochemical recurrence (BCR) rate, and continence rate at 12 months after surgery were reviewed and compared between the LRP and RALP groups. Result The operative outcomes revealed significantly less blood loss (143 mL vs. 306 mL, p < 0.001), shorter hospital stay (6.9 days vs. 8.7 days, p = 0.006), and shorter duration of Foley catheterization (9.3 days vs. 11.3 days, p < 0.001) in patients who underwent RALP. Major perioperative complications occurred in four LRP patients (4%), and none were observed in RALP patients. LRP and RALP had similar positive surgical margin rates ( p = 0.285) and BCR rates ( p = 0.88). RALP resulted in better continence recovery than LRP (55% vs. 82.5%, p = 0.003). Conclusion Patients who underwent RALP had better perioperative and functional outcomes. Oncologic outcomes were similar compared to patients who underwent LRP. [ABSTRACT FROM AUTHOR]

Background There was no consensus about the management of patients with urinary retention and elevated serum prostate-specific antigen (PSA) levels. This study aimed to determine whether concomitant transrectal ultrasound (TRUS)-guided biopsy and transurethral resection of prostate (TURP) is practical in patients with urinary retention and elevated serum PSA levels. Methods From March 2007 to May 2015, a total of 34 patients with urinary retention and elevated PSA (≥ 4 ng/mL) underwent concomitant TRUS-guided biopsy and TURP. The medical records were evaluated retrospectively, and data including PSA, prostate volume, TURP results, TRUS-guided biopsy results, length of hospitalization, and complications were collected. These patients were then compared with 40 patients with urinary retention who underwent TURP alone. Results The mean age of the patients was 71.6 years. The mean PSA levels were 16.9 ng/mL. Prostate cancer was detected in eight cases (23.5%): one case by TRUS-guided biopsy alone, two cases by TURP alone, and five cases by both TRUS-guided biopsy and TURP. Complications included fever in five patients (14.7%), recatheterization for urine retention in two patients (5.9%), urinary tract infection in two patients (5.9%), and de novo urge incontinence in seven patients (20.6%). The complication rate was not significantly increased compared with that of the patients who underwent TURP alone. Conclusion This study showed that concomitant TRUS-guided biopsy and TURP was safe and of possible clinical significance in urinary retention patients with elevated serum PSA. [ABSTRACT FROM AUTHOR]

Purpose: Glycine N-methyltransferase (GNMT) affects genetic stability by regulating the ratio of S-adenosylmethionine to S-adenosylhomocysteine, by binding to folate, and by interacting with environmental carcinogens. In Taiwanese men, GNMT was found to be a tumor susceptibility gene for prostate cancer. However, the association of GNMT with prostate cancer risk in other ethnicities has not been studied. It was recently reported that sarcosine, which is regulated by GNMT, increased markedly in metastatic prostate cancer. We hereby explored the association of GNMT polymorphisms with prostate cancer risk in individuals of European descent from the Health Professionals Follow-up Study (HPFS). Methods: A total of 661 incident prostate cancer cases and 656 controls were identified from HPFS. The GNMT short tandem repeat polymorphism 1 (STRP1), 4-bp insertion/deletion polymorphisms (INS/DEL) and the single nucleotide polymorphism rs10948059 were genotyped to test for their association with prostate cancer risk. Results: The rs10948059 T/T genotype was associated with a 1.62-fold increase in prostate cancer risk (95% confidence interval (CI): 1.18, 2.22) when compared with the C/C genotype. The STRP1 ≥16GAs/≥16GAs genotype was associated with decreased risk of prostate cancer when compared with the <16GAs/<16GAs genotype (odds ratio (OR) = 0.68; 95% CI: 0.46, 1.01). INS/DEL was not associated with prostate cancer risk. Haplotypes containing the rs10948059 T allele were significantly associated with increased prostate cancer risk. Conclusion: In men of European descent, the GNMT rs10948059 and STRP1 were associated with prostate cancer risk. Compared to the study conducted in Taiwanese men, the susceptibility GNMT alleles for prostate cancer had a reverse relationship. This study highlights the differences in allelic frequencies and prostate cancer susceptibility in different ethnicities. [ABSTRACT FROM AUTHOR]

Objective: We attempted to determine the association between a G/A polymorphism at position 158 of the prostate-specific antigen (PSA) gene and the risk of prostate cancer in Taiwanese men. Materials and Methods: We genotyped 149 prostate cancer patients and 176 healthy controls. Logistic regression was used to estimate the odd ratios (ORs) and confidence intervals (CIs). Results: The G allele was more frequent than the A allele in both cases and in controls. The A allele was not associated with a significantly higher risk of prostate cancer (odds ratio [OR] = 1.17, confidence interval = 0.78-1.76). GA (OR = 1.18) and AA (OR = 1.19) genotypes were not associated with a significantly higher risk of prostate cancer. In an analysis by disease aggressiveness, aggressive disease had a higher OR than that for nonaggressive disease (1.38 vs. 0.77); however, these associations were not statistically significant. Conclusions: No association was found between G/A polymorphism and the risk of prostate cancer. Larger studies are necessary to determine whether the A allele is associated with aggressive prostate cancer. [Copyright &y& Elsevier]