Alpha-L-Fucosidase Has Diagnostic Value in Prostate Cancer With “Gray-Zone PSA” and Inhibits Cancer Progression via Regulating Glycosylation

BackgroundThis study aimed to explore the diagnostic value of alpha-l-fucosidase (AFU) in prostate cancer (PCa) patients with “gray-zone PSA” and to investigate the correlation between AFU expression and clinicopathological characteristics of PCa patients.MethodsThe level of AFU and other necessary clinicopathological variables of patients were retrieved from electronic medical records. The transcriptome profiling and clinical information of PCa patients were obtained from The Cancer Genome Atlas (TCGA) database. The protein level of AFU in tissue was assessed by immunohistochemistry (IHC). All the data were processed by appropriate analysis methods. The p-value of <0.05 was considered statistically significant.ResultsAFU showed ideal diagnostic value for PCa with prostate-specific antigen (PSA) levels ranging from 4 to 10 ng/ml, and its optimal cutoffs were 19.5 U/L. Beyond this, low AFU expression was associated with high pathological grade, T stage and N stage, more postoperative residual tumors, and poor primary therapy outcome, as well as shorter progression-free interval. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis illustrated that FUCA1/FUCA2 exerted tumor-suppressive function by regulating the glycosylation.ConclusionsAFU (<19.5 U/L) could effectively distinguish the PCa from the patients with “gray-zone PSA”, and low expression of AFU was an independent unfavorable predictor for the clinicopathological characteristics of PCa patients.

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Soluble CD105 is prognostic of disease recurrence in prostate cancer patients

Endocrine Related Cancer ◽

10.1530/erc-19-0370 ◽

2020 ◽

Vol 27 (1) ◽

pp. 1-9

Author(s):

Veronica R Placencio-Hickok ◽

Anisha Madhav ◽

Sungjin Kim ◽

Frank Duong ◽

Bryan Angara ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Cancer Progression ◽

Early Stage ◽

Specific Antigen ◽

Cancer Recurrence ◽

Independent Set ◽

Disease Recurrence ◽

Primary Therapy ◽

Translational Study

While the overall 5-year survival rate for prostate cancer is near 100%, up to 35% of patients will develop recurrent disease. At the time of prostatectomy, prostate-specific antigen (PSA) is used to guide primary therapy with the goal of curative intervention. It can be valuable to know when primary therapy may not in fact be curative, so that subsequent adjuvant therapy can be administered at an early stage to limit progression. We examined prostate cancer patients with PSA ≤10 ng/mL that were all subjected to prostatectomy with at least 5 years of follow-up (n = 181). Based on data that endoglin (CD105) signaling in the tumor can contribute to prostate cancer progression, we examined the expression of soluble CD105 (sCD105) in the patient plasma. To determine the relation of plasma sCD105 measures to cellular CD105 in tissues, we tested an independent set of prostate cancer tissues and paired plasma (n = 31). Elevated sCD105 was found to be associated with recurrence-free survival of prostate cancer patients. Further, sCD105 levels in patient plasma were inversely correlated with cellular CD105 expression. This translational study supported preclinical data demonstrating the pro-tumorigenic capacity of cellular CD105 and provide a blood-based biomarker, sCD105, for prostate cancer recurrence in prostatectomy patients with PSA levels ≤10 ng/mL.

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Differential Expression of a Panel of Ten CNTN1-Associated Genes during Prostate Cancer Progression and the Predictive Properties of the Panel towards Prostate Cancer Relapse

Genes ◽

10.3390/genes12020257 ◽

2021 ◽

Vol 12 (2) ◽

pp. 257

Author(s):

Yan Gu ◽

Mathilda Jing Chow ◽

Anil Kapoor ◽

Xiaozeng Lin ◽

Wenjuan Mei ◽

...

Keyword(s):

Prostate Cancer ◽

Differential Expression ◽

Cancer Progression ◽

Lncap Cell ◽

Endocrine Resistance ◽

Gene Panel ◽

The Cancer Genome Atlas ◽

Cancer Center ◽

Poor Overall Survival ◽

Cell Renal Cell Carcinoma

Contactin 1 (CNTN1) is a new oncogenic protein of prostate cancer (PC); its impact on PC remains incompletely understood. We observed CNTN1 upregulation in LNCaP cell-derived castration-resistant PCs (CRPC) and CNTN1-mediated enhancement of LNCaP cell proliferation. CNTN1 overexpression in LNCaP cells resulted in enrichment of the CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_3 gene set that facilitates endocrine resistance in breast cancer. The leading-edge (LE) genes (n = 10) of this enrichment consist of four genes with limited knowledge on PC and six genes novel to PC. These LE genes display differential expression during PC initiation, metastatic progression, and CRPC development, and they predict PC relapse following curative therapies at hazard ratio (HR) 2.72, 95% confidence interval (CI) 1.96–3.77, and p = 1.77 × 10−9 in The Cancer Genome Atlas (TCGA) PanCancer cohort (n = 492) and HR 2.72, 95% CI 1.84–4.01, and p = 4.99 × 10−7 in Memorial Sloan Kettering Cancer Center (MSKCC) cohort (n = 140). The LE gene panel classifies high-, moderate-, and low-risk of PC relapse in both cohorts. Additionally, the gene panel robustly predicts poor overall survival in clear cell renal cell carcinoma (ccRCC, p = 1.13 × 10−11), consistent with ccRCC and PC both being urogenital cancers. Collectively, we report multiple CNTN1-related genes relevant to PC and their biomarker values in predicting PC relapse.

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Prostate cancer screening: A survey of medical students’ knowledge in Lome, Togo, and associated determinants in a resource-limited African context

SAGE Open Medicine ◽

10.1177/20503121211032812 ◽

2021 ◽

Vol 9 ◽

pp. 205031212110328

Author(s):

Tchin Darré ◽

Toukilnan Djiwa ◽

Tchilabalo Matchonna Kpatcha ◽

Albadia Sidibé ◽

Edoé Sewa ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Screening ◽

Medical Students ◽

Confidence Interval ◽

Prostate Cancer Screening ◽

Specific Antigen ◽

Digital Rectal Examination ◽

P Value ◽

Theoretical Knowledge ◽

Practical Level

Objectives: The aims of this study were to assess the knowledge of medical students in Lomé about these means of screening for prostate cancer in a context of limited resources and controversy about prostate cancer screening, and to identify the determinants associated with these results. Methods: This was a prospective descriptive and cross-sectional study conducted in the form of a survey of medical students regularly enrolled at the Faculty of Health Sciences of the University of Lomé for the 2019–2020 academic years. Results: Of the 1635 eligible students, 1017 correctly completed the form, corresponding to a rate of 62.20%. The average age was 22 ± 3.35 years. The sex ratio (M/F) was 2.5. Undergraduate students were the most represented (53.69%). Students who had not received any training on prostate cancer were the most represented (57.13%). Only 12.88% of the students had completed a training course in urology. Concerning the prostate-specific antigen blood test, there was a statistically significant relationship between the students’ knowledge and some of their socio-demographic characteristics, namely age (p value = 0.0037; 95% confidence interval (0.50–1.77)); gender (p value = 0.0034; 95% confidence interval (1.43–2.38)); study cycle (p value ˂ 0.0001; 95% confidence interval (0.56–5.13)) and whether or not they had completed a placement in a urology department (p value ˂ 0.0001; 95% confidence interval (0.49–1.55)). On the contrary, there was no statistically significant relationship between students’ knowledge of the digital rectal examination and their study cycle (p value = 0.082; 95% confidence interval (0.18–3.44)). Conclusion: Medical students in Lomé have a good theoretical knowledge and a fair practical level of the digital rectal examination clinical examination and an average theoretical knowledge and a below average practical level of prostate-specific antigen, increasing however along the curriculum in the context of prostate cancer screening.

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Comparative performance of MRI-derived PRECISE scores and delta-radiomics models for the prediction of prostate cancer progression in patients on active surveillance

European Radiology ◽

10.1007/s00330-021-08151-x ◽

2021 ◽

Author(s):

Nikita Sushentsev ◽

Leonardo Rundo ◽

Oleg Blyuss ◽

Tatiana Nazarenko ◽

Aleksandr Suvorov ◽

...

Keyword(s):

Prostate Cancer ◽

Active Surveillance ◽

Cancer Progression ◽

Predictive Value ◽

Machine Learning Algorithms ◽

Superior Performance ◽

Control Group ◽

P Value ◽

Lasso Regression

Abstract Objectives To compare the performance of the PRECISE scoring system against several MRI-derived delta-radiomics models for predicting histopathological prostate cancer (PCa) progression in patients on active surveillance (AS). Methods The study included AS patients with biopsy-proven PCa with a minimum follow-up of 2 years and at least one repeat targeted biopsy. Histopathological progression was defined as grade group progression from diagnostic biopsy. The control group included patients with both radiologically and histopathologically stable disease. PRECISE scores were applied prospectively by four uro-radiologists with 5–16 years’ experience. T2WI- and ADC-derived delta-radiomics features were computed using baseline and latest available MRI scans, with the predictive modelling performed using the parenclitic networks (PN), least absolute shrinkage and selection operator (LASSO) logistic regression, and random forests (RF) algorithms. Standard measures of discrimination and areas under the ROC curve (AUCs) were calculated, with AUCs compared using DeLong’s test. Results The study included 64 patients (27 progressors and 37 non-progressors) with a median follow-up of 46 months. PRECISE scores had the highest specificity (94.7%) and positive predictive value (90.9%), whilst RF had the highest sensitivity (92.6%) and negative predictive value (92.6%) for predicting disease progression. The AUC for PRECISE (84.4%) was non-significantly higher than AUCs of 81.5%, 78.0%, and 80.9% for PN, LASSO regression, and RF, respectively (p = 0.64, 0.43, and 0.57, respectively). No significant differences were observed between AUCs of the three delta-radiomics models (p-value range 0.34–0.77). Conclusions PRECISE and delta-radiomics models achieved comparably good performance for predicting PCa progression in AS patients. Key Points • The observed high specificity and PPV of PRECISE are complemented by the high sensitivity and NPV of delta-radiomics, suggesting a possible synergy between the two image assessment approaches. • The comparable performance of delta-radiomics to PRECISE scores applied by expert readers highlights the prospective use of the former as an objective and standardisable quantitative tool for MRI-guided AS follow-up. • The marginally superior performance of parenclitic networks compared to conventional machine learning algorithms warrants its further use in radiomics research.

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Carbonic Anhydrase I as a New Plasma Biomarker for Prostate Cancer

ISRN Oncology ◽

10.5402/2012/768190 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 5

Author(s):

Michiko Takakura ◽

Akira Yokomizo ◽

Yoshinori Tanaka ◽

Michimoto Kobayashi ◽

Giman Jung ◽

...

Keyword(s):

Prostate Cancer ◽

Carbonic Anhydrase ◽

Cancer Patients ◽

Plasma Proteins ◽

Specific Antigen ◽

Healthy Controls ◽

Gray Zone ◽

Plasma Biomarker ◽

Carbonic Anhydrase I ◽

Discrimination Rate

Serum prostate-specific antigen (PSA) levels ranging from 4 to 10 ng/mL is considered a diagnostic gray zone for detecting prostate cancer because biopsies reveal no evidence of cancer in 75% of these subjects. Our goal was to discover a new highly specific biomarker for prostate cancer by analyzing plasma proteins using a proteomic technique. Enriched plasma proteins from 25 prostate cancer patients and 15 healthy controls were analyzed using a label-free quantitative shotgun proteomics platform called 2DICAL (2-dimensional image converted analysis of liquid chromatography and mass spectrometry) and candidate biomarkers were searched. Among the 40,678 identified mass spectrum (MS) peaks, 117 peaks significantly differed between prostate cancer patients and healthy controls. Ten peaks matched carbonic anhydrase I (CAI) by tandem MS. Independent immunological assays revealed that plasma CAI levels in 54 prostate cancer patients were significantly higher than those in 60 healthy controls (, Mann-Whitney test). In the PSA gray-zone group, the discrimination rate of prostate cancer patients increased by considering plasma CAI levels. CAI can potentially serve as a valuable plasma biomarker and the combination of PSA and CAI may have great advantages for diagnosing prostate cancer in patients with gray-zone PSA level.

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Association of Caveolin-1 Expression With Prostate Cancer: A Systematic Review and Meta-Analysis

Frontiers in Oncology ◽

10.3389/fonc.2020.562774 ◽

2021 ◽

Vol 10 ◽

Author(s):

Pei Chen ◽

Yu-ling Zhang ◽

Bai Xue ◽

Guo-ying Xu

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Prognostic Value ◽

Meta Analysis ◽

Specific Antigen ◽

Intraepithelial Neoplasia ◽

Clinicopathological Characteristics ◽

Clinicopathological Feature ◽

Caveolin 1 ◽

The Relationship

PurposeThe prognostic value of caveolin-1 in prostate cancer remains uncertain. Hence, this meta-analysis was performed to evaluate the prognostic value of caveolin-1 in prostate cancer, as well as ascertain the relationship between caveolin-1 expression and clinicopathological characteristics of prostate cancer patients.MethodsThe PubMed, Embase, Chinese National Knowledge Infrastructure and Chinese Biology Medicine databases were electronically searched to retrieve published studies on caveolin-1 expression in prostate cancer. After study selection and data extraction, the meta-analysis was conducted using Review manager 5.3 software. Odds ratio (OR) with 95% confidence interval (CI) was used to estimate the pooled effect. Funnel plot was used to assess publication bias.ResultsA total of ten studies were enrolled, which included 3976 cases of prostate cancer, 72 cases of high-grade intraepithelial neoplasia (HGPIN), and 157 normal controls. Results of the meta-analysis showed that the positive rate of caveolin-1 expression in prostate cancer was 18.28 times higher than that in normal control (OR= 18.28, 95% CI: 9.02–37.04, p<0.01), and 4.73 times higher than that in HGPIN (OR= 4.73, 95% CI: 2.38–9.42, p<0.01). The relationship between caveolin-1 and clinicopathological characteristics of prostate cancer showed that the differences in caveolin-1 expression in patients with prostate-specific antigen (PSA) >10 vs. ≤ 10 (OR=2.09, 95% CI: 1.35–3.22, p<0.01), differentiation degree low vs. medium/high (OR=2.74, 95% CI: 1.84–4.08, p<0.01), TNM stage T3+T4 vs. T1+T2 (OR=2.77, 95% CI: 1.78–4.29, p<0.01), and lymph node metastasis present vs. absent (OR=2.61, 95% CI: 1.84–3.69, p<0.01) were statistically significant. The correlation analysis between caveolin-1 and the survival time of patients with prostate cancer demonstrated that caveolin-1 was closely related to the prognosis of prostate cancer patients (HR=1.50, 95% CI: 1.28–1.76, p<0.01).ConclusionCaveolin-1 is overexpressed in prostate cancer, which can serve as a risk factor and adverse clinicopathological feature of prostate cancer. Caveolin-1 can also predict poor survival in prostate cancer patients after radical prostatectomy.

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The role of the androgen receptor as a driver and mitigator of cellular stress

Journal of Molecular Endocrinology ◽

10.1530/jme-20-0057 ◽

2020 ◽

Vol 65 (2) ◽

pp. R19-R33

Author(s):

Dimitrios Doultsinos ◽

Ian Mills

Keyword(s):

Prostate Cancer ◽

Protein Synthesis ◽

Androgen Receptor ◽

Cancer Progression ◽

Prostate Gland ◽

Specific Antigen ◽

Nuclear Hormone Receptor ◽

Biological Processes ◽

Normal Prostate ◽

Mtor Activity

Prostate cancer is a high-incidence male cancer, which is dependent on the activity of a nuclear hormone receptor, the androgen receptor (AR). Since the AR is required for both normal prostate gland development and for prostate cancer progression, it is possible that prostate cancer evolves from perturbations in AR-dependent biological processes that sustain specialist glandular functions. The archetypal example of course is the use of prostate specific antigen (PSA), an organ-type specific component of the normal prostate secretome, as a biomarker of prostate cancer. Furthermore, localised prostate cancer is characterised by a low proliferative index and a heterogenous array of somatic mutations aligned to a multifocal disease pattern. We and others have identified a number of biological processes that are AR dependent and represent aberrations in significant glandular processes. Glands are characterised by high rates of metabolic activity including protein synthesis supported by co-dependent processes such as glycosylation, organelle biogenesis and vesicle trafficking. Impairments in anabolic metabolism and in protein folding/processing will inevitably impose proteotoxic and oxidative stress on glandular cells and, in particular, luminal epithelial cells for which secretion is their primary function. As cancer develops there is also significant metabolic dysregulation including impaired negative feedback effects on glycolytic and anabolic activity under conditions of hypoxia and heightened protein synthesis due to dysregulated PI 3-kinase/mTOR activity. In this review we will focus on the components of the AR regulome that support cancer development as well as glandular functions focussing on the unfolded protein response and on regulators of mTOR activity.

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Role of a novel race-related tumor suppressor microRNA located in frequently deleted chromosomal locus 8p21 in prostate cancer progression

Carcinogenesis ◽

10.1093/carcin/bgz058 ◽

2019 ◽

Vol 40 (5) ◽

pp. 633-642 ◽

Cited By ~ 3

Author(s):

Divya Bhagirath ◽

Thao Ly Yang ◽

Z Laura Tabatabai ◽

Varahram Shahryari ◽

Shahana Majid ◽

...

Keyword(s):

Prostate Cancer ◽

Tumor Suppressor ◽

Cell Lines ◽

Cancer Progression ◽

Specific Antigen ◽

Tumor Grade ◽

Clinical Samples ◽

Mesenchymal Transition ◽

Microrna Genes

Abstract The prostate cancer (PCa) genome is characterized by deletions of chromosome 8p21–22 region that increase significantly with tumor grade and are associated with poor prognosis. We proposed and validated a novel, paradigm-shifting hypothesis that this region is associated with a set of microRNA genes—miR-3622, miR-3622b, miR-383—that are lost in PCa and play important mechanistic roles in PCa progression and metastasis. Extending our hypothesis, in this study, we evaluated the role of a microRNA gene located in chromosome 8p—miR-4288—by employing clinical samples and cell lines. Our data suggests that (i) miR-4288 is widely downregulated in primary prostate tumors and cell lines; (ii) miR-4288 expression is lost in metastatic castration-resistant PCa; (ii) miR-4288 downregulation is race-related PCa alteration that is prevalent in Caucasian patients and not in African Americans; (iii) in Caucasians, miR-4288 was found to be associated with increasing tumor grade and high serum prostate-specific antigen, suggesting that miR-4288 downregulation/loss may be associated with tumor progression specifically in Caucasians; (iv) miR-4288 possess significant potential as a molecular biomarker to predict aggressiveness/metastasis; and (v) miR-4288 is anti-proliferative, is anti-invasive and inhibits epithelial-to-mesenchymal transition; and (vi) miR-4288 directly represses expression of metastasis/invasion-associated genes MMP16 and ROCK1. Thus, the present study demonstrates a tumor suppressor role for a novel miRNA located with a frequently lost region in PCa, strengthening our hypothesis that this locus is causally related to PCa disease progression via loss of microRNA genes. Our study suggests that miR-4288 may be a novel biomarker and therapeutic target, particularly in Caucasians.

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Abiraterone in patients with metastatic castration-resistant prostate cancer progressing after docetaxel and MDV3100.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.4554 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 4554-4554 ◽

Cited By ~ 6

Author(s):

Ecaterina Ileana ◽

Yohann Loriot ◽

Laurence Albiges ◽

Christophe Massard ◽

Aurore Blesius ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Progression ◽

Specific Antigen ◽

Patient Characteristics ◽

Preliminary Evidence ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Symptom Response ◽

Psa Response ◽

Metastatic Sites

4554 Background: Chemotherapy with docetaxel is the standard first-line treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). In patients progressing after docetaxel, both abiraterone and MDV3100 have yielded improved survival for patients with mCRPC. The efficacy of abiraterone in patients pre-treated with MDV 3100 is unknown. Methods: We investigated abiraterone-prednisone in 24 patients with cancer progression after docetaxel followed by MDV3100. All patients received abiraterone 1000 mg/day plus prednisone 10mg/day. Prostate-specific antigen (PSA) response, symptom response, and time to progression were assessed. Results: Patient characteristics were as follows: median age: 74 years (53-84), median PSA: 108 ng/mL (2-2541), metastatic sites: bone: all 24 patients, liver/lung: 6 patients (25%), and lymph nodes : 9 patients (38%). Five patients (21%) had a PSA decrease on abiraterone-prednisone. Three patients (13%) achieved a PSA response, defined as a decrease of >50% in PSA, confirmed after≥ 4 weeks. The duration of PSA response was 2, 3 and 4.5 months. Six patients (29%) had a symptomatic response on the pain score and analgesic consumption was decreased. Treatment was well tolerated. Abiraterone-prednisone was discontinued in one patient due to edema and hypokaliemia. Conclusions: This study shows preliminary evidence that abiraterone-prednisone yields activity in patients with mCRPC pretreated with docetaxel and MDV3100.

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Autophagic cell death with hydroxychloroquine in patients with hormone-dependent prostate-specific antigen progression after local therapy for prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.102 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 102-102 ◽

Cited By ~ 1

Author(s):

Mridula Annette George ◽

Tina M. Mayer ◽

Dirk Moore ◽

Chunxia Chen ◽

Eileen White ◽

...

Keyword(s):

Prostate Cancer ◽

Tumor Growth ◽

Prostate Specific Antigen ◽

Hormonal Therapy ◽

Doubling Time ◽

Specific Antigen ◽

Local Therapy ◽

Primary Therapy ◽

Response Change ◽

Early Tumor

102 Background: For patients who have a rising prostate-specific antigen value after definitive local therapy, androgen deprivation is a commonly employed option. However, immediate hormonal therapy has not been shown to alter the progression of the disease. Prior studies showed the dependence of early tumor growth and progression on anaerobic metabolism through glycolysis. Autophagy is conserved, genetically controlled catabolic response to starvation and stress whereby cells self-digest intracellular proteins and organelles by targeting them for degradation in lysosomes to generate energy and mitigate damage, thereby supporting cancer cell survival. Our hypothesis was that the autophagic inhibitor, hydroxychloroquine, when utilized in prostate cancer, would interfere with defective autophagy such that tumor growth will be slowed or stopped. Methods: Patients had rising PSA after primary therapy for PC, no radiographic evidence of metastasis, no (neo)adjuvant ADT within 3 months of enrollment and testosterone > 150 ng/dL. Hydroxychloroquine was dosed at 400 mg/day (cohort 1) or 600 mg/day (cohort 2). Endpoints were PSA response (change in slope of PSA rise by at least 25%, when log (PSA) is plotted vs. time). Results: 64 patients (36 cohort 1; 28 patients cohort 2) with median age 71(55-94) and baseline PSA was 3.25ng/ml (0.24- 45.69ng/ml) were enrolled in the study. 39 patients completed 6 months of hydroxychloroquine therapy and 44 patients completed 5 months of treatment. Out of 64 patients, 52 had at least 5 PSA measurements after the start of treatment, and we restrict our analysis to these patients. In 33 patients of these 52 (63%), the doubling time decreased after treatment began. In 12 of these 52 (23%), the “doubling time” turned negative, consistent with decreasing PSA value. Most common adverse events were diarrhea (26%), nausea (12%) and rash (12%). Conclusions: Hydroxychloroquine appears to have some activity in PSA progression after localized therapy with minimal toxicity. Given that hydroxychloroquine has limited side effects, this drug has the potential to augment responses to hormonal therapy or chemotherapy. Clinical trial information: NCT00726596.

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