scholarly journals Loss of miR-378 in prostate cancer, a common regulator of KLK2 and KLK4, correlates with aggressive disease phenotype and predicts the short-term relapse of the patients

2014 ◽  
Vol 395 (9) ◽  
pp. 1095-1104 ◽  
Author(s):  
Margaritis Avgeris ◽  
Konstantinos Stravodimos ◽  
Andreas Scorilas
Keyword(s):  
Prostate Cancer ◽  
Gleason Score ◽  
Cox Regression ◽  
Elevated Serum ◽  
Recurrence Risk ◽  
Tumor Stage ◽  
Short Term ◽  
Prostate Hyperplasia ◽  
Cox Regression Analysis ◽  
Improve Risk Stratification

Abstract A large number of prostate cancer (PCa) patients receive treatment without significant benefits, strengthening the need for accurate prognosis, which can be supported by the study of miRNAs. In silico specificity analysis was performed for the identification of miRNAs able to regulate KLK2 and KLK4 expression. Total RNA was extracted from prostate tissues obtained from PCa and benign prostate hyperplasia patients. Thereafter, RNA was polyadenylated and reverse transcribed to cDNA, which was used for qPCR analysis. miR-378 was predicted to target both KLK2 and KLK4 and downregulated levels detected in PCa patients (p=0.050). The reduction of miR-378 was correlated with higher Gleason score (p=0.018), larger diameter tumors (p=0.034), and elevated serum PSA (p=0.006). Regarding prognosis, miR-378 was able to improve risk stratification according to Gleason score or tumor stage, while higher risk to recur highlighted for the patients expressing lower miR-378 levels. Finally, the loss of miR-378 was able to predict the short-term relapse of ‘high’- and ‘very high’-recurrence-risk patients, independent of Gleason score, tumor stage, PSA, and age as indicated by Kaplan-Meier survival curves (p=0.030) and multivariate Cox regression analysis (p=0.018). In conclusion, loss of miR-378 expression increases the risk for PCa progression and relapse, despite active treatment.

scholarly journals Active Surveillance in Younger Men With Prostate Cancer

2017 ◽  
Vol 35 (17) ◽  
pp. 1898-1904 ◽  
Author(s):  
Michael S. Leapman ◽  
Janet E. Cowan ◽  
Hao G. Nguyen ◽  
Katsuto K. Shinohara ◽  
Nannette Perez ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Active Surveillance ◽  
Gleason Score ◽  
Cox Regression ◽  
Young Patients ◽  
Definitive Treatment ◽  
Primary Study ◽  
Study Objective ◽  
Cox Regression Analysis ◽  
Younger Age

Purpose The suitability of younger patients with prostate cancer (PCa) for initial active surveillance (AS) has been questioned on the basis of eventual treatment necessity and concerns of safety; however, the role of age on surveillance outcomes has not been well defined. Patients and Methods We identified men managed with AS at our institution with a minimum follow-up of 6 months. The primary study objective was to examine the association of age with risk of biopsy-based Gleason score upgrade during AS. We also examined the association of age with related end points, including overall biopsy-determined progression, definitive treatment, and pathologic and biochemical outcomes after delayed radical prostatectomy (RP), using descriptive statistics, the Kaplan-Meier method, and multivariable Cox proportional hazards regression. Results A total of 1,433 patients were followed for a median of 49 months; 74% underwent initial biopsy at a referring institution. Median age at diagnosis was 63 years, including 599 patients (42%) ≤ 60 years old and 834 (58%) > 60 years old. The 3- and 5-year biopsy-based Gleason score upgrade-free rates were 73% and 55%, respectively, for men ≤ 60 years old compared with 64% and 48%, respectively, for men older than 60 years ( P < .01). On Cox regression analysis, younger age was independently associated with lower risk of biopsy-based Gleason score upgrade (hazard ratio per 1-year decrease, 0.969 [95% CI, 0.956 to 0.983]; P < .01), and persisted upon restriction to men meeting strict AS inclusion criteria. There was no significant association between younger age and risk of definitive treatment or risk of biochemical recurrence after delayed RP. Conclusion Younger patient age was associated with decreased risk of biopsy-based Gleason score upgrade during AS but not with risk of definitive treatment in the intermediate term. AS represents a strategy to mitigate overtreatment in young patients with low-risk PCa in the early term.

Chromogranine A and neuron-specific enolase as the main predictors of survival for hormone-refractory prostate cancer (HRPC) patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15594-15594
Author(s):  
A. Banu ◽  
E. Banu ◽  
D. Dionysopoulos ◽  
J. Medioni ◽  
F. Scotte ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Regression Analysis ◽  
Gleason Score ◽  
Cox Regression ◽  
Neuron Specific Enolase ◽  
Cox Regression Analysis ◽  
Risk Of Death ◽  
Metastatic Sites ◽  
Ecog Ps ◽  
The Impact

15594 Background: Clinical studies suggested that the extent of neuro-endocrine differentiation in prostate cancer increases with tumor progression and the development of androgen refractory status. Chromogranine (CgA) and neuron-specific enolase (NSE) are currently explored as surrogate markers. Methods: Eligible chemonaive HRPC patients (pts) were required to have an ECOG performance status (PS) ≤ 2. Before chemotherapy initiation, we quantified NSE, CgA and PSA in the venous blood using commercial kits. We evaluated the impact of baseline NSE, CgA and PSA on overall survival (OS) using multivariate Cox regression analysis, stratified by chemotherapy regimen. Secondary, we studied the correlation between NSE, CgA, PSA and other important variables as age, Gleason score, hemoglobin, number of metastatic sites and ECOG PS. Results: Data of 39 consecutive HRPC pts treated between December 01–06 in a single French center were analyzed. Chemotherapy was docetaxel-based in 92% of pts. Median age was 71 years (range 51–86) and 79% of pts had bone metastases. Elevated NSE, CgA and PSA were observed in 6, 9 and 30% of pts and median levels were 10.8, 67 and 23.3 ng/mL, respectively. Gleason 8–10 was present in 49% of pts. Significant correlations were observed between NSE and the number of metastatic sites and between CgA and age, hemoglobin and ECOG PS. The baseline PSA was only correlated with Gleason score. Median OS for the entire cohort was 24.4 months (95% CI, 18.8–29.9). Two-year OS was 15% and only 19% of patients are dead. Univariate Cox regression analysis showed only a significant relationship between OS and baseline NSE: hazard ratio= 1.09 (95% CI, 1.03–1.16), P=0.006. No other known prognostic factors are related to outcome. A multivariate model including baseline NSE, CgA, ECOG PS and Gleason score showed a 15% rise of the risk of death related to NSE (borderline P value). Conclusions: NSE was the most powerful predictor of survival for HRPC pts. Our results emphasize the theory that cells secreting NSE are chemoresistant, with a negative impact on OS. No significant financial relationships to disclose.

scholarly journals Does perineural invasion in a radical prostatectomy specimen predict biochemical recurrence in men with prostate cancer?

2015 ◽  
Vol 9 (5-6) ◽  
pp. 252 ◽  
Author(s):  
Fairleigh Reeves ◽  
Christopher M. Hovens ◽  
Laurence Harewood ◽  
Shayne Battye ◽  
Justin S. Peters ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Regression Analysis ◽  
Radical Prostatectomy ◽  
Gleason Score ◽  
Biochemical Recurrence ◽  
Perineural Invasion ◽  
Cox Regression ◽  
Clinicopathological Parameters ◽  
Positive Surgical Margin ◽  
Cox Regression Analysis

Introduction: The ability of perineural invasion (PNI) in radical prostatectomy (RP) specimens to predict biochemical recurrence (BCR) is unclear. This study investigates this controversial question in a large cohort.Methods: A retrospective analysis was undertaken of prospectively collected data from 1497 men who underwent RP (no neoadjuvant therapy) for clinically localized prostate cancer. The association of PNI at RP with other clinicopathological parameters was evaluated. The correlation of clinicopathological factors and BCR (defined as prostate-specific antigen [PSA] >0.2 ng/mL) was investigated with univariable and multivariable Cox regression analysis in 1159 men.Results: PNI-positive patients were significantly more likely to have a higher RP Gleason score, pT3 disease, positive surgical margins, and greater cancer volume (p < 0.0005). The presence of PNI significantly correlated with BCR on univariable (hazard ratio 2.30, 95% confidence interval 1.50–3.55, p < 0.0005), but not multivariable analysis (p = 0.602). On multivariable Cox regression analysis the only independent prognostic factors were preoperative PSA, RP Gleason score, pT-stage, and positive surgical margin status. These findings are limited by a relatively short follow-up time and retrospective study design.Conclusions: PNI at RP is not an independent predictor of BCR. Therefore, routine reporting of PNI is not indicated. Future research should be targeted at the biology of PNI to increase the understanding of its role in prostate cancer progression.

scholarly journals PVT1 Expression Is a Predictor for Poor Survival of Prostate Cancer Patients

2021 ◽  
Vol 20 ◽  
pp. 153303382097161
Author(s):  
Jianhua Liu ◽  
Yanqing Li ◽  
Qiqi Zhang ◽  
Chaoxiang Lv ◽  
Mingwei Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Gleason Score ◽  
Roc Curve ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Cox Regression ◽  
Molecular Therapy ◽  
Vital Status ◽  
Cox Regression Analysis

Objective: Dysregulation of long noncoding RNA is associated with a variety of cancers and LncRNA has anticancer or carcinogenic activities. PVT1, as a long noncoding RNA, plays an important role in the development of cancer. Methods: We use R to download and analyze the data in TCGA database. ROC curve is generated to evaluate the significance of PVT1 expression for the diagnosis of prostate cancer. Chi-square test is used to test correlation between PVT1 expression and clinical pathological features. Survival curve and univariate and multivariate cox regression analysis is performed to compare differences in the effect on the survival rate between PVT1 high expression and low expression. Results: The expression of PTV1 in tumor tissues was significantly higher than that in normal tissues(P<2.2e-16). The difference of PTV1 expression was observed according to vital status (P = 0.0051) and Gleason score (P = 0.0012). The expression of PTV1 is significantly associated with T classification (P < 0.0001), N classification (P = 0.0499), PSA (P = 0.0001), Gleason Score (P < 0.0001), targeted molecular therapy (P = 0.0264) and vital status(P = 0.0036). The area under the ROC curve (AUC) was 0.860, which revealed PTV1 expression has excellent diagnostic value in prostate cancer. Patients with high PVT1 expression had a worse prognosis. Conclusions: PVT1 expression may be a biomarker for the diagnosis and prognosis of prostate cancer.

scholarly journals Prognostic Models for Patients With Gleason Score 9 Prostate Cancer: A Population-Based Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Jianhui Qiu ◽  
Desheng Cai ◽  
Zixin Wang ◽  
Jingcheng Zhou ◽  
Yanqing Gong ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Marital Status ◽  
Gleason Score ◽  
Cox Regression ◽  
Population Based ◽  
Competing Risk ◽  
Age At Diagnosis ◽  
Population Based Study ◽  
Cox Regression Analysis ◽  
Gleason Pattern

Purpose: Gleason score (GS) system is one of the most widely used histological grading methods for prostate cancer (PCa) all over the world. GS can be obtained by adding the primary Gleason pattern (GP) and secondary GP. Different proportions of GP 4 and GP 5 in prostate specimens can both lead to GS 9. In this study, we explored whether GP 5 + 4 or GP 4 + 5 was associated with different prognoses among patients with GS 9 PCa.Materials and methods: A retrospective population-based study was conducted on 10,124 subjects diagnosed with GS 9 PCa between 2004 and 2009 from the Surveillance, Epidemiology, and End Results program. A 1:1 propensity-score matching (PSM) was performed to balance the baseline characteristics between the GP 4 + 5 and 5 + 4 groups and to compare the prognoses between the two groups. Cox regression analysis and Fine-Gray competing risk regression models were adopted to screen the covariates significantly associated with all-cause mortality (ACM) and cancer-specific mortality (CAM).Results: GP 5 + 4 was associated with higher risks of ACM and CSM before or after PSM than GP 4 + 5. In the original cohort, there were eight independent predictors for ACM, which were age at diagnosis, race, AJCC NM stage, PSA levels, treatments, GP, and marital status, confirmed by the Cox analysis; and nine independent predictors for CSM, which were age at diagnosis, race, AJCC TNM stage, PSA levels, treatments, GP, and marital status, confirmed by the competing-risk model.Conclusion: GP 5 + 4 was associated with a poorer overall survival and cancer-specific survival compared with GP 4 + 5.

scholarly journals 5 Gleason score-associated gene signatures serve as novel biomarkers for identifying early recurring events and contributing to early diagnosis for Prostate Adenocarcinoma

2020 ◽  
Author(s):  
Lingyu Zhang ◽  
Yu Li ◽  
Weiwei Liu ◽  
Xuchu Wang ◽  
Ying Ping ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gleason Score ◽  
Cox Regression ◽  
Tnm Classification ◽  
Cox Proportional Hazards ◽  
The Cancer Genome Atlas ◽  
Prognostic Models ◽  
Diagnostic Efficiency ◽  
Cox Regression Analysis ◽  
Gene Signatures

Abstract Background: Prostate cancer (PCa) recurrence leads to much higher mortality than those without recurring events. Early and accurate laboratory diagnosis is particularly important for early identification of patients at high risk of recurrence and to benefit from additional systemic intervention. This study aimed to develop efficient and accurate Prostate Cancer diagnostic and prognostic biomarkers for the identification of initial tumor new events. Methods: Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas (TCGA) data portal were utilized to obtain differentially expressed genes (DEGs) and clinical trait information in PCa. WGCNA analysis obtained the most relevant clinical traits and genes enriched in several modules. Univariate Cox regression analysis and multivariate Cox proportional hazards (Cox-PH) model was employed to candidate gene signatures related to Disease-Free Interval (DFI). Internal and external cohort was utilized to test and validate the validity, accuracy, and clinical utility of prognostic models.Results: We constructed and optimized a valid and credible model for predicting patient outcomes, based on 5 Gleason score-associated gene signatures (ZNF695, CENPA, TROAP, BIRC5, KIF20A). Furthermore, ROC and Kaplan-Meier analysis revealed higher diagnostic efficiency for PCa and predictive effectiveness in tumor recurrence and metastasis. Calibration curve also revealed high prediction accuracy in internal TCGA cohort and external GEO cohort. The model was prognostically significant in the stratified cohort, including TNM classification and Gleason score, and was deemed to be an independent PCa prognostic factor, and superioring to other clinicopathological characteristics. On the other hand, we also measured the correlation between gene signatures’ expression and inflammation landscape. 5 gene signatures were significantly positively correlated with tumor purity and negatively correlated with the immersion levels of CD8+ T cells. Conclusions: Our study identified and validated 5 gene signatures as biomarkers for prostate cancer diagnosis, providing an assessment of DFI while predicting tumor progression, possibly providing novel theories for the treatment of prostate cancer.

Alpha-methylacyl-CoA Racemase and Hepsin as Urinary Prostate Cancer Markers

2015 ◽  
Vol 30 (4) ◽  
pp. 401-406 ◽  
Author(s):  
Wiktor Dariusz Sroka ◽  
Marek Adamowski ◽  
Piotr Słupski ◽  
Joanna Siódmiak ◽  
Piotr Jarzemski ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gleason Score ◽  
False Negative ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Tumor Stage ◽  
Urine Samples ◽  
True Positive ◽  
Prostate Hyperplasia ◽  
Before And After

Background Because of the numerous limitations of prostate-specific antigen (PSA), α-methylacyl-CoA racemase (AMACR) and hepsin have recently been suggested as potential biomarkers in prostate cancer (PC). This report presents a comparison study of the presence of AMACR and hepsin in urine collected before and after digital rectal examination (DRE) as a previously suggested diagnostic marker for PC. Methods Seventy-six urine samples (38 before and 38 after prostate massage) from patients with benign prostate hyperplasia (BPH) and 66 urine samples (33 before and 33 after prostate massage) from patients with PC were analyzed. PC was confirmed by prostate biopsy. Urinary levels of AMACR and hepsin were determined by ELISA and related to the tumor stage, Gleason score and PSA level. Results AMACR and hepsin levels in urine collected after prostate massage were higher only in the PC group. There were no correlations between AMACR levels, hepsin levels, tumor stage and Gleason score. AMACR and hepsin did not differentiate between BPH and PC with better true positive and false negative rates than serum PSA. Conclusions AMACR and hepsin were unable to diagnose PC with better true positive and false negative rates than PSA. An additional procedure combined with other markers should be applied for the reliable diagnosis of PC.

scholarly journals Prognostic Association between Common Laboratory Tests and Overall Survival in Elderly Men with De Novo Metastatic Castration Sensitive Prostate Cancer: A Population-Based Study in Canada

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2844
Author(s):  
Christopher J. D. Wallis ◽  
Bobby Shayegan ◽  
Scott C. Morgan ◽  
Robert J. Hamilton ◽  
Ilias Cagiannos ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Clinical Decision Making ◽  
Cox Regression ◽  
De Novo ◽  
Population Based ◽  
Population Based Study ◽  
Cox Regression Analysis ◽  
Lymphocyte Ratio ◽  
Laboratory Markers

De novo cases of metastatic prostate cancer (mCSPC) are associated with poorer prognosis. To assist in clinical decision-making, we aimed to determine the prognostic utility of commonly available laboratory-based markers with overall survival (OS). In a retrospective population-based study, a cohort of 3556 men aged ≥66 years diagnosed with de novo mCSPC between 2014 and 2019 was identified in Ontario (Canada) administrative database. OS was assessed by using the Kaplan–Meier method. Multivariate Cox regression analysis was performed to evaluate the association between laboratory markers and OS adjusting for patient and disease characteristics. Laboratory markers that were assessed include neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), albumin, hemoglobin, serum testosterone and PSA kinetics. Among the 3556 older men with de novo mCSPC, their median age was 77 years (IQR: 71–83). The median survival was 18 months (IQR: 10–31). In multivariate analysis, a statistically significant association with OS was observed with all the markers (NLR, PLR, albumin, hemoglobin, PSA decrease, reaching PSA nadir and a 50% PSA decline), except for testosterone levels. Our findings support the use of markers of systemic inflammation (NLR, PLR and albumin), hemoglobin and PSA metrics as prognostic indicators for OS in de novo mCSPC.

Perioperative Activation of Disseminated Tumor Cells in Bone Marrow of Patients With Prostate Cancer

2009 ◽  
Vol 27 (10) ◽  
pp. 1549-1556 ◽  
Author(s):  
Dorothea Weckermann ◽  
Bernhard Polzer ◽  
Thomas Ragg ◽  
Andreas Blana ◽  
Günter Schlimok ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Tumor Cells ◽  
Cox Regression ◽  
Systemic Disease ◽  
Disseminated Tumor Cells ◽  
Comparative Genomic ◽  
Prognostic Impact ◽  
Primary Tumors ◽  
Cox Regression Analysis

Purpose The outcome of prostate cancer is highly unpredictable. To assess the dynamics of systemic disease and to identify patients at high risk for early relapse we followed the fate of disseminated tumor cells in bone marrow for up to 10 years and genetically analyzed such cells isolated at various stages of disease. Patients and Methods Nine hundred bone marrow aspirates from 384 patients were stained using the monoclonal antibody A45-B/B3 directed against cytokeratins 8, 18, and 19. Log-rank statistics and Cox regression analysis were applied to determine the prognostic impact of positive cells detected before surgery (244 patients) and postoperatively (214 patients). Samples from primary tumors (n = 55) and single disseminated tumor cells (n = 100) were analyzed by comparative genomic hybridization. Results Detection of cytokeratin-positive cells before surgery was the strongest independent risk factor for metastasis within 48 months (P < .001; relative risk [RR], 5.5; 95% CI, 2.4 to 12.9). In contrast, cytokeratin-positive cells detected 6 months to 10 years after radical prostatectomy were consistently present in bone marrow with a prevalence of approximately 20% but had no influence on disease outcome. Characteristic genotypes of cytokeratin-positive cells were selected at manifestation of metastasis. Conclusion Cytokeratin-positive cells in the bone marrow of prostate cancer patients are only prognostically relevant when detected before surgery. Because we could not identify significant genetic differences between pre- and postoperatively isolated tumor cells before manifestation of metastasis, we postulate the existence of perioperative stimuli that activate disseminated tumor cells. Patients with cytokeratin-positive cells in bone marrow before surgery may therefore benefit from adjuvant therapies.

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