scholarly journals Small Extracellular Vesicle-Derived microRNAs Stratify Prostate Cancer Patients According to Gleason Score, Race and Associate with Survival of African American and Caucasian Men

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5236
Author(s):  
Hamdy E. A. Ali ◽  
Mohamed S. A. Gaballah ◽  
Rofaida Gaballa ◽  
Shahenda Mahgoub ◽  
Zeinab A. Hassan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
Gleason Score ◽  
Proportional Hazards ◽  
Extracellular Vesicle ◽  
Cox Proportional Hazards ◽  
Independent Prognostic Marker ◽  
Clinical Biomarkers ◽  
Caucasian Men ◽  
Prognostic Utility

The utility of small extracellular vesicles (sEVs)-derived microRNAs (miRs) to segregate prostate cancer (PCa) patients according to tumor aggressiveness and ancestral background has not been fully investigated. Thus, we aimed to determine the diagnostic and prognostic utility of sEV-associated miRs in identifying aggressive PCa in African American (AA) and Caucasian (CA) men. Using a training cohort, miR profiling was performed on sEVs isolated from plasma of PCa patients. Top-ranked sEV-associated miRs were then validated in 150 plasma samples (75 AA and 75 CA) collected from two independent cohorts; NIH (n = 90) and Washington University (n = 60) cohorts. Receiver operating characteristic (ROC) curve, Kaplan–Meier and Cox proportional hazards regression were used to assess these miRs as clinical biomarkers. Among nine top-ranked sEV-associated miRs, miR-6068 and miR-1915-3p were enriched in sEVs collected from PCa patients compared to healthy volunteers. Moreover, miR-6716-5p and miR-3692-3p segregated AA from CA men and low from high Gleason score (GS), respectively. Upregulation of sEV-associated miR-1915-3p, miR-3692-3p and miR-5001-5p was associated with improved survival time, and only miR-1915-3p was associated with longer recurrence-free survival (RFS) as an independent prognostic marker. Taken together, we identified novel sEV-associated miRs that can differentiate PCa patients from normal, AA from CA and high from low GS and predicts RFS.

Evaluating the impact of African American ancestry among men with localized prostate cancer treated with radical prostatectomy.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 41-41
Author(s):  
Daniel Canter ◽  
Julia E. Reid ◽  
Maria Latsis ◽  
Margaret Variano ◽  
Shams Halat ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
Radical Prostatectomy ◽  
Gleason Score ◽  
Metastatic Disease ◽  
Proportional Hazards ◽  
Clinical Stage ◽  
Cox Proportional Hazards ◽  
Significant Difference ◽  
The Impact

41 Background: Prostate cancer (PC) is the most common male malignancy. Prior data has suggested that African American (AA) men present with more aggressive disease relative to men of other ancestries. Here, we examined the effects of ancestry on clinical and molecular measures of disease aggressiveness as well as pathologic outcomes in men treated with radical prostatectomy (RP) for localized PC. Methods: Data was collected from patients undergoing RP at the Ochsner Clinic from 2006 to 2011. Formalin−fixed paraffin embedded biopsy tissue was analyzed for the RNA expression of 31 cell cycle progression (CCP) genes and 15 housekeeping genes to obtain a CCP score (a validated molecular measure of PC aggressiveness). Cancer of the Prostate Risk Assessment (CAPRA) scores were also determined based on clinicopathologic features at the time of diagnosis. Clinical (Gleason score, tumor stage, CAPRA score) and molecular (CCP score) measures of disease aggressiveness were compared based on ancestry (AA versus non−AA). Cox proportional hazards models were used to test association of ancestry to biochemical recurrence (BCR) and progression to metastatic disease. Fisher’s exact and Wilcoxon rank sum tests were used to compare ancestries. Results: A total of 384 patients were treated with RP, including 133 (34.8%) AA men. At the time of diagnosis, the median age was 62 years (interquartile range (IQR) 56, 66) and PSA was 5.4 ng/mL (IQR 4.2, 7.6). When compared by ancestry, there were no significant differences in biopsy Gleason score (p = 0.26), clinical stage (p = 0.27), CAPRA score (p = 0.58), or CCP score (p = 0.87). In addition, there was no significant difference in the risk of BCR between ancestries (p = 0.55). Only non−AA men progressed to metastatic disease within the ten years of follow−up. Conclusions: Contrary to prior reports, these data appears to indicate that men of AA ancestry do not necessarily present with or develop a more biologically aggressive form of PC. Although these data represents only one institution’s experience, it contains a highly robust AA population compared to prior reports. Further research is required to account for the discrepancy in the previously published literature.

scholarly journals Pathologic and biochemical outcomes among African American and Caucasian men with low-risk prostate cancer in the search database: Implications for active surveillance candidacy.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 76-76
Author(s):  
Michael S. Leapman ◽  
Stephen J. Freedland ◽  
William J Aaronson ◽  
Christopher J. Kane ◽  
Martha K. Terris ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
Biochemical Recurrence ◽  
Proportional Hazards ◽  
Clinical Stage ◽  
Cox Proportional Hazards ◽  
Low Risk ◽  
Equal Access ◽  
Caucasian Race ◽  
Caucasian Men

76 Background: Racial disparities in the incidence and risk profile of prostate cancer (PCa) at diagnosis among African American (AA) men are well reported, however it remains unclear whether AA race is independently associated with adverse pathological findings among men with clinical low risk disease. Methods: We conducted a retrospective analysis among 895 men, with clinical low risk (Gleason 3+3, clinical stage ≤T2a, PSA≤10 ng/mL) treated with immediate radical prostatectomy within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. We evaluated clinical and demographic characteristics by AA or Caucasian race. Associations between AA versus Caucasian race with pathologic Gleason upgrade (≥3+4), major upgrade (≥4+3), upstage (pT3a or higher), margin status and biochemical recurrence (BCR) were examined using chi-square, logistic regression, log-rank, and Cox proportional hazards analyses. Results: We identified 355 AA and 540 Caucasian men with low-risk tumors within the SEARCH cohort followed for a median of 6.3 (IQR 3.8-8.9). AA men were younger (mean 59.5vs. 62.0 years), and had higher median PSA (5.5 vs. 5.1). Following adjustment for relevant covariates, AA race was not significantly associated with pathological upgrade (OR 1.335, 95% CI 0.936-1.905, p=0.111), major upgrade (OR 0.561, 95% CI 0.300-1.049, p=0.070), upstaging (OR 1.111, 95% CI 0.670-1.844, p=0.683), or positive surgical margins (OR 1.046, 95% CI 0.732-1.494, p=0.806). The 5-year recurrence-free survival rates were 73.4% and 78.4% for AA and Caucasian men, respectively (log-rank p=0.178). After adjustment for clinical and pathological characteristics, AA race was not significantly associated with BCR (HR 1.1.054, 95% CI 0.814-1.501, p=0.521). Conclusions: In a cohort of low-risk men treated with prostatectomy within an equal access health system with a high representation of AA men, no significant differences were observed in the rates of pathologic upgrading, upstaging or biochemical recurrence. These data support continued use of AS in AA. Upgrading and upstaging remain concerning possibilities for all men regardless of race.

Is expanded radiographic criteria for clinically positive lymph nodes associated with outcome in pathologically node positive prostate cancer?

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 126-126
Author(s):  
Chad A. Reichard ◽  
Justin Gregg ◽  
Tharakeswara Bathala ◽  
Mary F. Achim ◽  
John W. Davis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lymph Nodes ◽  
Gleason Score ◽  
Biochemical Recurrence ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Free Survival ◽  
Outcome Differences ◽  
Baseline Psa ◽  
Positive Lymph Nodes

126 Background: Patients with pN1 prostate cancer (PCa) have heterogeneous outcomes largely dependent on variables only known post-treatment. Traditionally, the size criteria for clinically positive pelvic adenopathy is axial diameter of 10mm. We employed expanded radiographic criteria (ERC) to evaluate for association with differences in outcome differences. Methods: 187 men treated with RP BPLND for PCa from 2001-2013 were identified as pN1. Imaging studies were re-reviewed by a single radiologist (TB) for nodes that were considered positive if they were 8mm or greater in size OR if they were 6mm or greater in size AND either rounded, asymmetrical OR heterogeneously enhancing. This yielded a group of 34 cN1 patients by ERC. Time to biochemical recurrence (BCR) was compared between cN0 and cN1 patients by K-M method. Cox proportional hazards modeling was used to determine association of baseline PSA, node status, adjuvant therapy, Gleason score, positive margins, and ECR with time to BCR and overall survival (OS). Results: Median age (61 v 59 p = 0.3), baseline PSA (8.7 v 11.1 p = 0.2), and positive margin rate (33% vs 32% p = 0.9) did not differ between cN0 and cN1 patients. Median number of positive LNs was higher in the cN1 group (2.7 v 1.8) p = 0.03. Median biochemical recurrence free survival did not differ between groups (3.3 vs 1.8 years p = 0.3) (Fig1). Only Gleason score was associated with shorter BCR free survival HR 1.3 (95%CI 1.0-1.62, p = 0.047). cN1 disease with expanded radiographic criteria did not predict BCR (HR 1.03, 95CI 0.62-171, p = 0.9) or ACM (HR 0.46, 95CI, 0.1-2.12, p = 0.3). Conclusions: Expanded radiographic criteria for clinically positive lymph nodes was not associated with BCR-free survival or OS in a group of pN1 PCa patients. Further study is required to determine if cN1 status based on expanded clinical criteria or more sensitive imaging methods is associated with outcome differences.

scholarly journals The UGT1 locus is a determinant of prostate cancer recurrence after prostatectomy

2014 ◽  
Vol 22 (1) ◽  
pp. 77-85 ◽  
Author(s):  
Isabelle Laverdière ◽  
Christine Flageole ◽  
Étienne Audet-Walsh ◽  
Patrick Caron ◽  
Yves Fradet ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Proportional Hazards ◽  
Prognostic Significance ◽  
Cancer Recurrence ◽  
Cox Proportional Hazards ◽  
Estrogen Metabolism ◽  
Nucleotide Polymorphisms ◽  
Functional Polymorphisms ◽  
Risk Alleles ◽  
Caucasian Men

The prognostic significance of common deletions in uridine diphospho-glucuronosyltransferase 2B (UGT2B) genes encoding sex steroid metabolic enzymes has been recently recognized in localized prostate cancer (PCa) after radical prostatectomy (RP). However, the role of germline variations at theUGT1locus, encoding half of all human UGTs and primarily involved in estrogen metabolism, remains unexplored. We investigated whether variants ofUGT1are potential prognostic markers. We studied 526 Caucasian men who underwent RP for clinically localized PCa. Genotypes of patients for 34 haplotype-tagged single-nucleotide polymorphisms (htSNPs) and 11 additional SNPs across theUGT1locus previously reported to mark common variants including functional polymorphisms were determined. The risk of biochemical recurrence (BCR) was estimated using adjusted Cox proportional hazards regression and Kaplan–Meier analysis. We further investigated whether variants are associated with plasma hormone levels by mass spectrometry. In multivariable models, seven htSNPs were found to be significantly associated with BCR. A greater risk was revealed for fourUGT1intronic variants with hazard ratios (HRs) of 1.59–1.88 (P<0.002) for htSNPs inUGT1A10,UGT1A9, andUGT1A6. Conversely, decreased BCR was associated with three htSNPs in introns ofUGT1A10andUGT1A9(HR=0.56–058;P≤0.01). An unfavorableUGT1haplotype comprising all risk alleles, with a frequency of 14%, had a HR of 1.68 (95% CI=1.13–2.50;P=0.011). Significant alteration in circulating androsterone levels was associated with this haplotype, consistent with changes in hormonal exposure. This study provides the first evidence, to our knowledge, that germline polymorphisms ofUGT1are potential predictors of recurrence of PCa after prostatectomy.

Clinical outcomes following biochemical recurrence among patients with Gleason score 9-10 prostate adenocarcinoma.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 102-102
Author(s):  
Kiri A Sandler ◽  
Fang-I Chu ◽  
Jay P. Ciezki ◽  
Richard Stock ◽  
Gregory Stephen Merrick ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gleason Score ◽  
Salvage Therapy ◽  
Biochemical Recurrence ◽  
Proportional Hazards ◽  
Incidence Rates ◽  
Cox Proportional Hazards ◽  
External Beam Radiation ◽  
Time Interval ◽  
Beam Radiation

102 Background: Patients with Gleason score (GS) 9-10 prostate cancer (PCa) have a high risk of early biochemical recurrence (BCR). Salvage therapy options differ depending on the upfront management strategy. Patients who received upfront surgery (RP) may be curable with salvage external beam radiation therapy (EBRT). However those who underwent EBRT or EBRT with a brachytherapy boost (EBRT+BT) are less likely to receive local salvage therapy and are commonly treated with androgen deprivation therapy (ADT). In this study, we examine the risk of distant metastases (DM) and prostate-cancer specific mortality (PCSM) among patients with GS 9-10 PCa who had BCR following RP, EBRT, or EBRT+BT. Methods: 712 patients with GS 9-10 PCa treated between 2000-2013 at 12 institutions who had BCR were included (346 RP, 282 EBRT, 84 EBRT+BT). Time to DM and PCSM were compared between groups using Cox proportional hazards models with propensity score adjustment. Propensity scores were calculated using age, T-stage, PSA, and GS. Results: In patients who had a BCR, incidence rates of DM and PCSM after RP were 40% and 28%. Rates after EBRT were 60% and 46% and after EBRT+BT were 49% and 31%. Median times to DM and PCSM were 3.5 and 4.9 years after RP, 3.7 and 5.1 years after EBRT, and 3.3 and 6.8 years after EBRT+BT. The rates of local salvage RT and systemic salvage therapy among RP patients were 38% and 59%, respectively. Local and systemic salvage rates were 5% and 31% for EBRT patients and 5% and 28% for EBRT+BT patients. EBRT patients had a shorter time interval to DM compared with RP (HR 1.4, p = .02) and EBRT+BT (HR 1.9, p < .01). EBRT patients also had a shorter time interval to PCSM compared with RP (HR 1.5, p = .02). Conclusions: Among patients with GS 9-10 PCa who experience BCR after definitive management, those treated with EBRT have a shorter time interval to DM and PCSM compared with RP and EBRT+BT. While this analysis is confounded by the differential thresholds for diagnosing a BCR after different modalities, it does suggest that outcomes following BCR after EBRT+BT and RP are similar. It also suggests that extreme dose escalation delays the onset of DM and PCSM even after BCR, when compared with conventionally-dosed EBRT alone.

scholarly journals Comparison of germline mutations in African American and Caucasian men with metastatic prostate cancer

The Prostate ◽  
2021 ◽  
Author(s):  
Elisa M. Ledet ◽  
Earle F. Burgess ◽  
Alexandra O. Sokolova ◽  
Ellen B. Jaeger ◽  
Whitley Hatton ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
Metastatic Prostate Cancer ◽  
Germline Mutations ◽  
Caucasian Men

scholarly journals Risk and Timing of Cardiovascular Disease After Androgen-Deprivation Therapy in Men With Prostate Cancer

2015 ◽  
Vol 33 (11) ◽  
pp. 1243-1251 ◽  
Author(s):  
Sean O'Farrell ◽  
Hans Garmo ◽  
Lars Holmberg ◽  
Jan Adolfsson ◽  
Pär Stattin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cardiovascular Disease ◽  
Androgen Deprivation Therapy ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Androgen Deprivation ◽  
Gnrh Agonists ◽  
Cvd Risk ◽  
Comparison Cohort ◽  
Using Data

Purpose Findings on the association between risk of cardiovascular disease (CVD) and the duration and type of androgen-deprivation therapy (ADT) in men with prostate cancer (PCa) are inconsistent. Methods By using data on filled drug prescriptions in Swedish national health care registers, we investigated the risk of CVD in a cohort of 41,362 men with PCa on ADT compared with an age-matched, PCa-free comparison cohort (n = 187,785) by use of multivariable Cox proportional hazards regression models. Results From 2006 to 2012, 10,656 men were on antiandrogens (AA), 26,959 were on gonadotropin-releasing hormone (GnRH) agonists, and 3,747 underwent surgical orchiectomy. CVD risk was increased in men on GnRH agonists compared with the comparison cohort (hazard ratio [HR] of incident CVD, 1.21; 95% CI, 1.18 to 1.25; and orchiectomy: HR, 1.16; 95% CI, 1.08 to 1.25). Men with PCa on AA were at decreased risk (HR of incident CVD, 0.87; 95% CI, 0.82 to 0.91). CVD risk was highest during the first 6 months of ADT in men who experienced two or more cardiovascular events before therapy, with an HR of CVD during the first 6 months of GnRH agonist therapy of 1.91 (95% CI, 1.66 to 2.20), an HR of CVD with AA of 1.60 (95% CI, 1.24 to 2.06), and an HR of CVD with orchiectomy of 1.79 (95% CI, 1.16 to 2.76) versus the comparison cohort. Conclusion Our results support that there should be a solid indication for ADT in men with PCa so that benefit outweighs potential harm; this is of particular importance among men with a recent history of CVD.

scholarly journals Differential expression of Annexin 2, SPINK1, and Hsp60 predict progression of prostate cancer through bifurcated WHO Gleason score categories in African American men

The Prostate ◽  
2018 ◽  
Vol 78 (11) ◽  
pp. 801-811 ◽  
Author(s):  
Desta A. Beyene ◽  
Tammey J. Naab ◽  
Norma F. Kanarek ◽  
Victor Apprey ◽  
Ashwini Esnakula ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
Differential Expression ◽  
Gleason Score ◽  
African American Men ◽  
Annexin 2
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