scholarly journals Promoter Methylation in APC, RUNX3, and GSTP1 and Mortality in Prostate Cancer Patients

2009 ◽  
Vol 27 (19) ◽  
pp. 3161-3168 ◽  
Author(s):  
Lorenzo Richiardi ◽  
Valentina Fiano ◽  
Loredana Vizzini ◽  
Laura De Marco ◽  
Luisa Delsedime ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Promoter Methylation ◽  
A Priori ◽  
Methylation Status ◽  
Specific Antigen ◽  
Prostate Cancer Progression ◽  
Increased Risk ◽  
In The Beginning

Purpose There is a need to better understand prostate cancer progression and identify new prognostic markers for this tumor. We investigated the association between promoter methylation in a priori selected genes and survival in two independent large series of prostate cancer patients. Methods We followed up with two cohorts of patients (216 patients diagnosed in 1982 to 1988 and 243 patients diagnosed in 1993 to 1996) diagnosed at one hospital pathology ward in Turin, Italy. DNA was obtained from paraffin-embedded tumor tissues and evaluated for promoter methylation status in glutathione S-transferase (GSTP1), adenomatous polyposis coli (APC), and runt-related transcription factor 3 (RUNX3). Results The two cohorts had different prevalences of methylation in APC (P = .047), GSTP1 (P = .002), and RUNX3 (P < .001). Methylation in APC was associated with an increased risk of prostate cancer–specific mortality (hazard ratio [HR] = 1.42; 95% CI, 0.98 to 2.07 in the 1980s cohort; HR = 1.57; 95% CI, 0.95 to 2.62 in the 1990s cohort; HR = 1.49; 95% CI, 1.11 to 2.00 in the two cohorts combined). In subgroup analyses, the HRs were higher among patients with a Gleason score less than 8 (HR = 1.52; 95% CI, 0.85 to 2.73 in the 1980s cohort; HR = 2.09; 95% CI, 1.02 to 4.28 in the 1990s cohort). Methylation in RUNX3 was associated with prostate cancer mortality only in the 1990s cohort, and methylation in GSTP1 did not predict mortality in either cohort. Conclusion The pattern of hypermethylation may have changed after the introduction of prostate-specific antigen testing in the beginning of the 1990s. Promoter methylation in APC was identified as a marker for prostate cancer progression.

scholarly journals Embigin Promotes Prostate Cancer Progression by S100A4-Dependent and-Independent Mechanisms

Cancers ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 239 ◽  
Author(s):  
I Ruma ◽  
Rie Kinoshita ◽  
Nahoko Tomonobu ◽  
Yusuke Inoue ◽  
Eisaku Kondo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Immunoglobulin Superfamily ◽  
Prostate Cancer Progression ◽  
Transmembrane Glycoprotein ◽  
Mtorc1 Signaling ◽  
Ampk Activity ◽  
In Vivo Growth

Embigin, a transmembrane glycoprotein belonging to the immunoglobulin superfamily, is involved in prostate and mammary gland development. As embigin’s roles in cancer remain elusive, we studied its biological functions and interaction with extracellular S100A4 in prostate cancer progression. We found by a pull-down assay that embigin is a novel receptor for S100A4, which is one of the vital cancer microenvironment milleu. Binding of extracellular S100A4 to embigin mediates prostate cancer progression by inhibition of AMPK activity, activation of NF-κB, MMP9 and mTORC1 signaling, and inhibition of autophagy, which increase prostate cancer cell motility. We also found that embigin promotes prostate cancer growth, spheroid- and colony-forming ability, and survival upon chemotherapy independently of S100A4. An in vivo growth mouse model confirmed the importance of embigin and its cytoplasmic tail in mediating prostate tumor growth. Moreover, embigin and p21WAF1 can be used to predict survival of prostate cancer patients. Our results demonstrated for the first time that the S100A4-embigin/AMPK/mTORC1/p21WAF1 and NF-κB/MMP9 axis is a vital oncogenic molecular cascade for prostate cancer progression. We proposed that embigin and p21WAF1 could be used as prognostic biomarkers and a strategy to inhibit S100A4-embigin binding could be a therapeutic approach for prostate cancer patients.

Variation in UDP glucouronyltransferase (UGT) genes associated with prostate cancer mortality.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 44-44
Author(s):  
M. Kohli ◽  
D. W. Mahoney ◽  
H. S. Chai ◽  
D. W. Hillman ◽  
D. R. Rider ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Advanced Prostate Cancer ◽  
Cox Regression ◽  
Prostate Cancer Progression ◽  
Androgen Ablation ◽  
Principle Components Analysis ◽  
Specific Mortality ◽  
Cancer Specific Mortality

44 Background: We investigated the association of germline genetic variation in hormone biosynthesis and metabolism genes with prostate cancer specific mortality in a cohort of advanced prostate cancer patients. Methods: We successfully genotyped 852 single nucleotide polymorphisms (SNPs) from 97 genes in a cohort of 267 advanced prostate cancer patients at the time of progression to castration recurrence (CRPC) during on-going androgen ablation. Tagging SNPs with minor allele frequency (MAF) of >5% and r2 ≥0.8 were selected from HapMap, NIEHS and Seattle SNP databases. Medical records were queried for cause of death. The primary endpoint of time to prostate cancer specific mortality (PCSM), was pre-defined as time from development of CRPC to death from prostate cancer progression. Principle components analysis was used for gene-levels tests, and to account for multiple testing, we calculated the false discovery rate (FDR). For SNP level results, hazard ratios (HR) and 95% confidence intervals (CI) were estimated using cox regression. Results: The median age of the cohort was 72 years at CRPC. 43% had a Gleason score (GS)=8-10, 33% a GS=7, and 24% a GS<7. After a median follow-up of 1.8 years (IQ range: 0.8–3.3 years), 139 patients died, of which 107 were due to prostate cancer progression. In unadjusted gene level analyses, UGT1A7 (p=0.0059; FDR=0.19), UGT1A10 (p=0.0017; FDR=0.17) and UGT1A3 (p=0.0037; FDR=0.18) were associated with PCSM. After adjusting for age and GS, SNPs strongly associated with PCSM are listed in the Table . Conclusions: Variation in UGT genes involved in hormone metabolism yield prognostic information in CRPC. Further validation is needed to develop these as prognostic biomarkers. [Table: see text] No significant financial relationships to disclose.

The Combined Percentage of Gleason Patterns 4 and 5 Is the Best Predictor of Cancer Progression After Radical Prostatectomy

2005 ◽  
Vol 23 (13) ◽  
pp. 2911-2917 ◽  
Author(s):  
Liang Cheng ◽  
Michael O. Koch ◽  
Beth E. Juliar ◽  
Joanne K. Daggy ◽  
Richard S. Foster ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Cancer Patients ◽  
Gleason Score ◽  
Cancer Progression ◽  
Tumor Volume ◽  
High Grade ◽  
Cox Regression Analysis ◽  
Total Tumor Volume ◽  
Increased Risk

Purpose Clinical outcome is variable in prostate cancer patients treated with radical prostatectomy. The Gleason histologic grade of prostatic adenocarcinoma is one of the strongest predictors of biologic aggressiveness of prostate cancer. We evaluated the significance of the relative proportion of high-grade cancer (Gleason patterns 4 and/or 5) in predicting cancer progression in prostate cancer patients treated with radical prostatectomy. Patients and Methods Radical prostatectomy specimens from 364 consecutive prostate cancer patients were totally embedded and whole mounted. Various clinical and pathologic characteristics were analyzed. All pathologic data, including Gleason grading variables, were collected prospectively. Results A multiple-factor analysis was performed that included the combined percentage of Gleason patterns 4 and 5, Gleason score, tumor stage, surgical margin status, preoperative prostate-specific antigen (PSA), extraprostatic extension, and total tumor volume. Using Cox regression analysis with bootstrap resampling for predictor selection, we identified the combined percentage of Gleason patterns 4 and 5 (P < .0001) and total tumor volume (P = .009) as significant predictors of PSA recurrence. Conclusion The combined percentage of Gleason patterns 4 and 5 is one of the most powerful predictors of patient outcome, and appears superior to conventional Gleason score in identifying patients at increased risk of disease progression. On the basis of our results, we recommend that the combined percentage of Gleason patterns 4 and 5 be evaluated in radical prostatectomy specimens. The amount of high-grade cancer in a prostatectomy specimen should be taken into account in therapeutic decision making and assessment of patient prognosis.

scholarly journals Linking obesogenic dysregulation to prostate cancer progression

2015 ◽  
Vol 4 (4) ◽  
pp. R68-R80 ◽  
Author(s):  
Renea A Taylor ◽  
Jennifer Lo ◽  
Natasha Ascui ◽  
Matthew J Watt
Keyword(s):  
Prostate Cancer ◽  
Adipose Tissue ◽  
Cancer Progression ◽  
Prostate Gland ◽  
The Body ◽  
Endocrine Function ◽  
Low Grade ◽  
Prostate Cancer Progression ◽  
Cancer Aggressiveness ◽  
Increased Risk

The global epidemic of obesity is closely linked to the development of serious co-morbidities, including many forms of cancer. Epidemiological evidence consistently shows that obesity is associated with a similar or mildly increased incidence of prostate cancer but, more prominently, an increased risk for aggressive prostate cancer and prostate cancer-specific mortality. Studies in mice demonstrate that obesity induced by high-fat feeding increases prostate cancer progression; however, the mechanisms underpinning this relationship remain incompletely understood. Adipose tissue expansion in obesity leads to local tissue dysfunction and is associated with low-grade inflammation, alterations in endocrine function and changes in lipolysis that result in increased delivery of fatty acids to tissues of the body. The human prostate gland is covered anteriorly by the prominent peri-prostatic adipose tissue and laterally by smaller adipose tissue depots that lie directly adjacent to the prostatic surface. We discuss how the close association between dysfunctional adipose tissue and prostate epithelial cells might result in bi-directional communication to cause increased prostate cancer aggressiveness and progression. However, the literature indicates that several ‘mainstream’ hypotheses regarding obesity-related drivers of prostate cancer progression are not yet supported by a solid evidence base and, in particular, are not supported by experiments using human tissue. Understanding the links between obesity and prostate cancer will have major implications for the health policy for men with prostate cancer and the development of new therapeutic or preventative strategies.

scholarly journals High-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
David P. Labbé ◽  
Giorgia Zadra ◽  
Meng Yang ◽  
Jaime M. Reyes ◽  
Charles Y. Lin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
High Fat Diet ◽  
Cellular Proliferation ◽  
Saturated Fat ◽  
Prostate Cancer Progression ◽  
Transcriptional Program ◽  
High Fat ◽  
Metabolic Alterations ◽  
Increased Risk

Abstract Systemic metabolic alterations associated with increased consumption of saturated fat and obesity are linked with increased risk of prostate cancer progression and mortality, but the molecular underpinnings of this association are poorly understood. Here, we demonstrate in a murine prostate cancer model, that high-fat diet (HFD) enhances the MYC transcriptional program through metabolic alterations that favour histone H4K20 hypomethylation at the promoter regions of MYC regulated genes, leading to increased cellular proliferation and tumour burden. Saturated fat intake (SFI) is also associated with an enhanced MYC transcriptional signature in prostate cancer patients. The SFI-induced MYC signature independently predicts prostate cancer progression and death. Finally, switching from a high-fat to a low-fat diet, attenuates the MYC transcriptional program in mice. Our findings suggest that in primary prostate cancer, dietary SFI contributes to tumour progression by mimicking MYC over expression, setting the stage for therapeutic approaches involving changes to the diet.

scholarly journals Soluble CD105 is prognostic of disease recurrence in prostate cancer patients

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.

scholarly journals 18F-PSMA-1007 and 18F-fluorocholine PET/CT in prostate cancer progression diagnostics. First comparative experience

2019 ◽  
Vol 15 (3) ◽  
pp. 70-76
Author(s):  
N. A. Meshcheriakova ◽  
M. B. Dolgushin ◽  
A. I. Pronin ◽  
V. B. Matveev ◽  
A. A. Odzharova ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Specific Antigen ◽  
Bone Lesions ◽  
Prostate Cancer Progression ◽  
Radical Treatment ◽  
Positron Emission ◽  
Pet Ct ◽  
Computed Tomography Scans ◽  
Changes Detection

Background. Prostate cancer progression remains as a major problem among patients after their radical treatment. During last years a broad spectrum radiopharmaceuticals had developed to reveal the cause of biochemical recurrence.Objective: the comparison of 18F-fluorocholine and 18F-prostate-specific membrane antigen-1007 (18F-PSMA-1007) diagnostic abilities for the prostate cancer progression detection.Materials and methods. In this study had been included 18F-fluorocholine and 18F-PSMA-1007 PET/CT (positron emission tomography combined with computed tomography) scans of 9 patients after radical treatment with increased prostate-specific antigen (PSA) level (range 0.10–9.06 ng/ml).Results. 18F-PSMA-1007-PET/CT detected lesions in 7 (77.8 %) out of 9 patients, after radical prostatectomy and brachytherapy, in comparison with negative 18F-fluorocholine-PET/CT results in all cases.Conclusion. In this pilot study, 18F-PSMA-1007-PET/CT has showed high potential in pathological changes detection among patients with increased PSA level (minimum 0.10 ng/ml) and demonstrated the advantages in comparison with 18F-fluorocholine-PET/CT, especially in terms of revealing local recurrence and metastatic lymph nodes, as well as, in bone lesions early detection.

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