Circulating miR-337-3p as a novel biomarker for prostate cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5087-5087
Author(s):  
Manuel Valladares Ayerbes ◽  
Vanessa Medina Villaamil ◽  
Sara Martinez Breijo ◽  
Isabel Santamarina Cainzos ◽  
Guadalupe Aparicio ◽  
...  

5087 Background: Recent studies have demonstrated that the aberrant expression of microRNAs (miRNAs)is related with the development of prostate cancer (PCa). Detection of circulating tumor cells (CTC) may provide diagnostic and prognostic information inPCa. The purpose is identifying circulating miRNAs potentially useful for CTC detection in patients with PCa. Methods: In the first study phase we examined blood levels of 92 miRNAs in 49 patients grouped in pools by risk classification: low-risk 42.8%, intermediate-risk 22.5% and high-risk 34.7% and healthy volunteers (N=10) using SYBR-green-based microARN RT-qPCR arrays (Exiqon). Prostate cancer diagnosis was obtained by transrectalultrasound guided biopsy of 10 cores, PSA and digital rectal examination was done previously. In the second study phase using quantitative real-time polymerase chain reaction (qPCR) by TaqMan Human MicroRNAAssays (Life Technologies), we compared the expression levels of miRNAs in blood samples from 34 patients of low-risk, 31 of intermediate-risk, 18 of high-risk localized disease and 22 healthy volunteers paired by age with cases. Receiver-operator characteristic (ROC) curve was used. Results: Blood samples from patients with low, intermediate, high-risk and healthy controls exhibit distinct circulating miRNA signatures. microRNAsdifferential expressed between risk groups (p<0.01) (low, intermediate and high) and control group: 0microARNs upregulated (MU), 12 MU and 68 MU respectively. Highlight the significantlyoverexpression in the intermediate risk group and maintained at the high-risk of microRNAs: 337-3p[247 PicTar predictions (PTP)], 330-3p (307 PTP) and 218 (551 PTP). Preliminary results of the second study phase showed that the median level of miRNA,337-3p was significantly higher in patients with high-risk than that in healthy controls (p=.001). ROC curve analyses indicated that this blood miRNA may beuseful for discriminating patients with high-risk from healthy controls (AUC=.724). Conclusions: miRNAs in the circulation are relatively stable, very accessible, low invasive and easily testable biomarkers. Our preliminary promisingresults suggest miR-337-3p as novel stable blood-based marker for PCa detection.

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Neda Gholizadeh ◽  
Peter B. Greer ◽  
John Simpson ◽  
Jonathan Goodwin ◽  
Caixia Fu ◽  
...  

Abstract Background Current multiparametric MRI (mp-MRI) in routine clinical practice has poor-to-moderate diagnostic performance for transition zone prostate cancer. The aim of this study was to evaluate the potential diagnostic performance of novel 1H magnetic resonance spectroscopic imaging (MRSI) using a semi-localized adiabatic selective refocusing (sLASER) sequence with gradient offset independent adiabaticity (GOIA) pulses in addition to the routine mp-MRI, including T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI) and quantitative dynamic contrast enhancement (DCE) for transition zone prostate cancer detection, localization and grading. Methods Forty-one transition zone prostate cancer patients underwent mp-MRI with an external phased-array coil. Normal and cancer regions were delineated by two radiologists and divided into low-risk, intermediate-risk, and high-risk categories based on TRUS guided biopsy results. Support vector machine models were built using different clinically applicable combinations of T2WI, DWI, DCE, and MRSI. The diagnostic performance of each model in cancer detection was evaluated using the area under curve (AUC) of the receiver operating characteristic diagram. Then accuracy, sensitivity and specificity of each model were calculated. Furthermore, the correlation of mp-MRI parameters with low-risk, intermediate-risk and high-risk cancers were calculated using the Spearman correlation coefficient. Results The addition of MRSI to T2WI + DWI and T2WI + DWI + DCE improved the accuracy, sensitivity and specificity for cancer detection. The best performance was achieved with T2WI + DWI + MRSI where the addition of MRSI improved the AUC, accuracy, sensitivity and specificity from 0.86 to 0.99, 0.83 to 0.96, 0.80 to 0.95, and 0.85 to 0.97 respectively. The (choline + spermine + creatine)/citrate ratio of MRSI showed the highest correlation with cancer risk groups (r = 0.64, p < 0.01). Conclusion The inclusion of GOIA-sLASER MRSI into conventional mp-MRI significantly improves the diagnostic accuracy of the detection and aggressiveness assessment of transition zone prostate cancer.


2021 ◽  
Vol 8 ◽  
Author(s):  
Mike Wenzel ◽  
Felix Preisser ◽  
Benedikt Hoeh ◽  
Maria N. Welte ◽  
Clara Humke ◽  
...  

Objective: To analyze the influence of biopsy Gleason score on the risk for lymph node invasion (LNI) during pelvic lymph node dissection (PLND) in patients undergoing radical prostatectomy (RP) for intermediate-risk prostate cancer (PCa).Materials and Methods: We retrospectively analyzed 684 patients, who underwent RP between 2014 and June 2020 due to PCa. Univariable and multivariable logistic regression, as well as binary regression tree models were used to assess the risk of positive LNI and evaluate the need of PLND in men with intermediate-risk PCa.Results: Of the 672 eligible patients with RP, 80 (11.9%) men harbored low-risk, 32 (4.8%) intermediate-risk with international society of urologic pathologists grade (ISUP) 1 (IR-ISUP1), 215 (32.0%) intermediate-risk with ISUP 2 (IR-ISUP2), 99 (14.7%) intermediate-risk with ISUP 3 (IR-ISUP3), and 246 (36.6%) high-risk PCa. Proportions of LNI were 0, 3.1, 3.7, 5.1, and 24.0% for low-risk, IR-ISUP1, IR-ISUP 2, IR-ISUP-3, and high-risk PCa, respectively (p &lt; 0.001). In multivariable analyses, after adjustment for patient and surgical characteristics, IR-ISUP1 [hazard ratio (HR) 0.10, p = 0.03], IR-ISUP2 (HR 0.09, p &lt; 0.001), and IR-ISUP3 (HR 0.18, p &lt; 0.001) were independent predictors for lower risk of LNI, compared with men with high-risk PCa disease.Conclusions: The international society of urologic pathologists grade significantly influence the risk of LNI in patients with intermediate- risk PCa. The risk of LNI only exceeds 5% in men with IR-ISUP3 PCa. In consequence, the need for PLND in selected patients with IR-ISUP 1 or IR-ISUP2 PCa should be critically discussed.


2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 82-82
Author(s):  
Ann Caroline Raldow ◽  
Danjie Zhang ◽  
Ming-Hui Chen ◽  
Michelle H. Braccioforte ◽  
Brian Joseph Moran ◽  
...  

82 Background: Active surveillance (AS) is considered appropriate for patients with low-risk prostate cancer (PC) and a life expectancy of at least 10 years. However, with grade migration following the 2005 International Society of Urologic Pathology consensus conference, AS may also be an initial option for men with favorable intermediate-risk PC. We estimated and compared the risk of PC-specific mortality (PCSM) following high dose radiation therapy and androgen deprivation therapy as appropriate amongst men with low, favorable intermediate, unfavorable intermediate, and high-risk PC. Methods: The study consisted of 6,595 consecutively treated men (median age: 68 years) with localized or locally advanced PC at the Chicago PC Center between 1997 and 2013. Fine and Gray competing risks regression analyses (table) were used to assess the risk of PCSM in men with favorable intermediate, unfavorable intermediate or high-risk compared to low-risk PC, adjusting for age at and year of treatment. Results: After median follow-up of 7.76 years, 820 men died: 72 of PC. While men with favorable intermediate-risk did not have significantly increased risk of PCSM as compared to low-risk PC (adjusted hazard ratio (HR) 1.28, 0.63-2.62 95% confidence interval (CI), p-value 0.49), men with high (adjusted HR 9.91, 5.48-17.94 95% CI, p-value <0.0001) or unfavorable intermediate-risk PC (adjusted HR 3.17, 1.60-6.30, p-value 0.001) did. Eight-year point estimates of PCSM were low: 0.68% [0.32-1.31% 95% CI] and 0.44% [0.25-0.75% 95% CI] for men with favorable intermediate and low-risk PC, respectively. Conclusions: Men with low and favorable intermediate-risk PC have similar and low estimates of PCSM during the first decade following standard management. These results provide evidence to support AS as an initial approach for men with favorable intermediate-risk PC. [Table: see text]


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16555-e16555
Author(s):  
Nancy P. Mendenhall ◽  
William Wong ◽  
Curtis Bryant ◽  
Sujay A. Vora ◽  
Randal H. Henderson ◽  
...  

e16555 Background: The ProtecT trial underscores the importance of treatment in men with prostate cancer and life expectancies > 10 years and the validity of radiation therapy (RT). RT can be given with photons or protons (PT). To address the controversy of which is better, clinical outcomes of photon-based intensity modulated RT (IMRT) and PT cohorts from 2 institutions were directly compared. Methods: Under respective IRB approvals, data from 2 cohorts were analyzed. The first was 301 men treated with ultrasound image guided IMRT from 2000-05 to 75.6 Gy in 42 fractions. The second was 1214 men treated with fiducial image guided PT from 2006-10 to 78 CGE in 39 fractions. Median age and followup were 74 y and 7.2 y for IMRT and 66 y and 5.6 y for PT. Hormone therapy (ADT) was used with IMRT and PT, respectively, in 3% and 7% of low-risk patients, 25% and 9.9% of intermediate-risk, and 91% and 57.8% of high-risk. Comparative endpoints were age-stratified 5-year (5Y) survival (OS), ≥ grade 3 gastrointestinal (GI) and urologic (GU) toxicity, and 5Y freedom from biochemical progression (FFBP). Results: There was a lower prevalence of GI (1.3% vs 0.1%, p = 0.0065) and GU (4.3% vs 0.1%, p < 0.0001) toxicity at last follow-up in the PT group. In the IMRT and PT cohorts, OS rates were 90.8% and 88.7% in men ≥75 (p = 0.4083). In men < 75, OS rates were 91.6% and 97.5% in the IMRT and PT low-risk patients (p = 0.003), 92.1% and 95.5% in the IMRT and PT intermediate-risk (p = 0.0535), and 92.0% and 90.0% (p = 0.4975) in the IMRT and PT high-risk. In the IMRT and PT cohorts, respectively, FFBP rates were 92.2% and 98.9% for low-risk patients (p < 0.0001), 87.3% and 94.5% for intermediate-risk patients(p = 0.0226), and 80.3% and 74.4% for high-risk patients (p = 0.5154). Conclusions: In this retrospective comparison of outcomes in cohorts of men treated with IMRT and PT for prostate cancer, FFBP rates were better with PT for men with low- and intermediate-risk disease and similar in men with high-risk disease despite longer and more frequent use of ADT in the IMRT cohort. This study underscores the difficulty of comparing retrospective series, with differences noted in age, RT dose, and ADT use between cohorts. However, the magnitude of improvement with PT is intriguing and warrants prospective testing.


2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 181-181
Author(s):  
M. M. Kim ◽  
K. E. Hoffman ◽  
L. B. Levy ◽  
S. J. Frank ◽  
S. Choi ◽  
...  

181 Background: A competing risks analysis was undertaken to identify patient subgroups at greatest risk of dying from prostate cancer (CAP) after treatment with definitive external beam radiation therapy (RT) +/− androgen deprivation therapy (ADT) in the PSA era, and to determine which factors predict for survival from disease. Methods: A total of 2,675 men with localized CAP treated with RT +/− ADT at M. D. Anderson Cancer Center from 1987-2007 were evaluated. Prostate cancer-specific mortality (PCSM) and other cause mortality rates were calculated after stratifying patients according to NCCN risk group, RT dose, use of ADT, and age at treatment. In total, 21% had low-risk, 40% had intermediate-risk, and 39% had high-risk disease. Multivariate analysis (MVA) was performed using Cox regression modeling. Results: Median age was 68.5 years and median follow-up was 6.4 years. For patients with low-risk disease, only 0.2% died of CAP 10 years after treatment. None of the low-risk patients <70 years old who received ≥72 Gy died of CAP. The majority of deaths in the intermediate-risk group were also due to other causes; men ≥70 years old who received <72 Gy had the highest 10-year PCSM (5%). High-risk patients <70 years old who received <72 Gy without ADT had similar 10-year rates of CAP (15.2%) and non-CAP (18.5%) mortality. Men with high-risk disease <70 years old treated with higher doses >72 Gy were twice as likely to die from non-CAP causes (15.9%) than die from CAP (8.6%). In older men ≥70 years old with high risk disease, dose-escalation with ADT reduced 10-year PCSM from 14% to 4%, and most deaths were due to other causes (41% and 20%). On MVA, dose (p=0.002), ADT (p=0.007), PSA (p<0.0001) and Gleason score (p<0.0001) were predictive of PCSM in the high-risk group. Conclusions: Men with low- and intermediate-risk CAP treated with definitive RT are unlikely to die of disease. PCSM is higher in men with high-risk disease but can be reduced with dose escalation and ADT, although patients are still twice as likely to die of other causes. No significant financial relationships to disclose.


2020 ◽  
Vol 27 (6) ◽  
Author(s):  
S. Parimi ◽  
S. Bondy ◽  
M. Aparicio ◽  
K. Sunderland ◽  
J. Cho ◽  
...  

Introduction Prostate cancer remains the 3rd leading cause of cancer-related mortality in Canadian men, and yet screening for prostate cancer continues to be controversial because the majority of men diagnosed with prostate cancer do not die of the disease. It also remains uncertain whether treatment of cases that can be treated with curative intent alters the mortality rate. There are very few studies describing the presenting stage, risk groups, and survival after diagnosis for men dying of prostate cancer in the literature. In this study, we explored these characteristics for all men who died of prostate cancer in British Columbia between 2013 and 2015. Methods The population-based BC Cancer databases were used to identify all patients diagnosed between Jan­uary 2013 and December 2015 who died of prostate cancer. Patient, tumour, and treatment characteristics were collected, and the risk grouping for each tumour was determined. The proportion of cases in each risk group at the time of diagnosis was determined. Survival time from diagnosis to death was calculated for all patients and for each risk group using the Kaplan–Meier method. Results A total of 1256 patients died of prostate cancer. Of patients who presented with metastatic disease, 57.2% presented with a Gleason score of 8 or more, compared with only 35.7% of patients who presented with nonmetastatic disease (p < 0.0001). The presenting stage and risk group of those dying of prostate cancer were as follows: 32% met­astatic disease, 3% regional (defined as node-positive), 39% localized high risk, 9% localized intermediate risk, 4% localized low risk, 6% localized not otherwise specified, and 7% unknown. Therefore, 80.3% of those with a known risk group presented with either localized high-risk, regional, or metastatic disease at diagnosis. The median survival times from diagnosis to death were 12 years for localized low-risk, 10 years for localized intermediate-risk, 6.5 years for localized high-risk, 4 years for regional, and 1.7 years for metastatic disease at diagnosis. Conclusions This population-based analysis demonstrates that patients with localized high-risk, regional, or metastatic disease at diagnosis constitute the overwhelming majority of patients who die of prostate cancer in British Columbia. Unless these disease states can reliably be identified at an earlier low- or intermediate-risk localized state in the future, it is unlikely that treatment of localized low- and intermediate-risk cancer will have an impact on sur­vival. Furthermore, patients with de novo metastatic disease had identifiable risk factors of a higher prostate-specific antigen and Gleason score. Further studies are required to confirm these results.


2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
C Desai ◽  
S A Ehsanullah ◽  
A Bhojwani ◽  
A Dhanasekaran

Abstract Introduction The Prostate Cancer Research Foundation – Stichting Wetenschappelijk Onderzoek Prostaatkanker group has devised the European Randomized Study of Screening for Prostate Cancer (CaP) Risk Calculator 3 (ERSPC-RC3) tool which aims to increase prostate cancer detection rates and avoid unnecessary prostate biopsies. We report the external validation and accuracy of the ERSPC-RC3 in our UK cohort. Method Retrospective data was collected for patients who had prostate biopsy at a multi-centre district general hospital over an 18-month period. The ERSPC-RC3 was applied to identify the probability of a positive biopsy for CaP (Gleason score ≥7). Results Out of 121 TRUS biopsies, 78 patients met the ERSPC-RC3 inclusion criteria. Patients were stratified as low-risk (detectable CaP risk &lt;12.5%) n = 10, intermediate-risk (detectable CaP risk 12.5-20%) n = 8, and high-risk (detectable CaP risk &gt;20%) n = 60 groups. All low-risk patients had a benign histology. Gleason 7 CaP was found in 37.5% from the intermediate-risk group and 41.7% in the high-risk group respectively. Conclusions Our results demonstrate that using ERSPC-RC3 could have prevented 44% (n = 34) of patients from having unnecessary biopsies. We recommend the use of ERSPC-RC3 to risk stratify patients being investigated for suspected CaP.


2019 ◽  
Author(s):  
Minh-Phuong Huynh-Le ◽  
Tor Åge Myklebust ◽  
Christine H. Feng ◽  
Roshan Karunamuni ◽  
Tom Børge Johannesen ◽  
...  

AbstractBackgroundOptimal prostate cancer (PCa) screening strategies will focus on men most likely to have potentially-lethal, localized disease. Age-specific incidence rates (ASIRs) for clinical risk groups could guide risk-stratified screening.ObjectiveDetermine ASIRs and proportions of PCa diagnoses in Norway for modern risk-group and Gleason score categories.Design, Setting, and ParticipantsAll men diagnosed with PCa in Norway in 2014-2017 (n=20,356).Outcome Measurements and Statistical AnalysisPatients were assigned to clinical risk groups: low, favorable-intermediate, unfavorable-intermediate, high, regional, and metastatic, using Gleason score and clinical stage. Associations were assessed between age and (1) Gleason score (including Gleason 3+4 and 4+3) and (2) PCa risk group. Risk-group ASIRs were calculated by multiplying the overall Norwegian ASIR by the proportions observed for each category.ResultsOlder age was significantly associated with higher Gleason score and more advanced disease. For example, among men aged 55-59, 65-69, 75-79, and 85-89 years, the percentage with Gleason 8-10 disease was 16.5%, 23.4%, 37.2%, and 59.9%, respectively (p<0.001); the percentage with at least high-risk disease was 29.3%, 39.1%, 60.4%, and 90.6%, respectively. Corresponding percentages for low-risk PCa were 24.0%, 17.9%, 10.2%, and 4.1% (p<0.001). The respective maximum ASIRs (per 100,000 men) for low-risk, favorable-intermediate-risk, unfavorable-intermediate-risk, high-risk, regional, and metastatic disease were: 157.1, 183.8, 194.8, 408.3, 172.3, and 330.0; incidence for low-risk and favorable-intermediate-risk PCa peaked before age 70, while more advanced categories peaked after 70. At age 75-79 years, the ASIR of high-risk disease was approximately 6 times greater than at 55-59 years.ConclusionsRisk of clinically-significant, localized PCa increases with age. Healthy older men may be among those most likely to benefit from PCa screening.


2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 54-54 ◽  
Author(s):  
Shiro Hinotsu ◽  
Hideyuki Akaza ◽  
Osamu Ogawa ◽  
Mototsugu Oya ◽  
Tadaichi Kitamura ◽  
...  

54 Background: In Japan, the J-CaP database was established in 2001 when the Japan Study Group of Prostate Cancer (J-CaP Study Group), commenced a study to gather information about hormone therapy administered to Japanese patients and to analyze the outcomes of treatment. From the results of prostate cancer registry conducted by Japanese Urological Association revealed that 45% of localized prostate cancer patients diagnosed in the year of 2000 treated by hormonal therapy in Japan. The J-CaP database is the largest cohort of over 20,000 prostate cancer patients treated by hormonal therapy. Therefore, the objective of the current study was to estimate the outcome of hormonal therapy for the localized prostate cancer patients in the J-CaP database. Methods: The study cohort included 9,127 men with localized prostate cancer who treated by hormonal therapy. All patients were diagnosed by biopsy as having prostate cancer and began to receive hormonal therapy between January 2001 and December 2003. In this study, initial hormonal treatment contained anti-androgen monotherapy, surgical castration only, LHRH agonist monothrerapy, LHRH agonist plus short-term anti-androgen, surgical castration plus anti-androgen, and LHRH agonist plus anti-androgen. All patients evaluated risk category of D’Amico classification. The percentage of Low-risk, intermediate-risk, and high-risk was 19%, 22%, and 59% of men, respectively. Prognosis analyses were performed using Kaplan–Meier methods. Progression-free survival and overall survival were estimated for each risk classification. Results: After a median follow-up of 2.9 years (interquartile range, 1.5-5.3 years) and five year progression-free survival of low-risk, intermediate-risk and high risk were 74.5%, 68.1%, and 57.1%, respectively. The five-year overall survival of low-risk, intermediate-risk, and high risk were 90.0%, 87.2%, and 81.8%, respectively. Conclusions: Comparing the results of radical prostatectomy in US, the five-year progression free survival was 54.6% in high-risk patients. Japanese patients with localized prostate cancer who treated hormonal therapy were comparable outcome of radical treatment in US considering the patients’ risk classification.


2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 51-51
Author(s):  
Chunde Li ◽  
Zhuochun Peng ◽  
Lambert Skoog ◽  
Henrik Hellborg ◽  
Inga-lill Wingmo ◽  
...  

51 Background: For prostate cancer patients, prostate cancer specific and non-prostate cancer specific survival have the same importance. This study aimed at identifying expression biomarkers that can predict prostate cancer specific, non-prostate cancer specific and overall survival at diagnosis. Methods: Selected ESCGPs (embryonic stem cell gene predictors) and control genes were analyzed by multiplex quantitative PCR using prostate fine-needle aspiration samples taken at diagnosis from a Swedish cohort of 189 prostate cancer patients diagnosed between 1986 and 2000. Of all patients, 97.9% had overall and cancer-specific survival data and 77.9% were primarily treated only by hormone therapy. The cohort was divided into one discovery and two validation subsets. Univariate and multivariate Cox proportional hazard ratios and Kaplan-Meier plots were used for the survival analysis. A published dataset was used for external validation. Results: An expression signature of F3, VGLL3 and IGFBP3, was sufficient to categorize the patients into high-risk, intermediate-risk and low-risk subtypes. The median overall survival of the subtypes was 3.23, 4.00 and 9.85 years respectively. The difference corresponded to HRs of 5.86 (95% CI 2.91-11.78, P<0.001) for the high-risk and 3.45 (95% CI 1.79-6.66, P<0.001) for the intermediate-risk compared to the low-risk subtype. This signature is significant in correlation to overall, cancer-specific and non-cancer specific survival in both univariate and multivariate analyses including common clinical parameters. Conclusions: These results suggest that these novel expression biomarkers and the expression signature could be used to improve the accuracy of the currently available clinical tools for predicting overall, cancer-specific and non-cancer specific survival and selecting patients with potential survival benefit from hormone treatment.


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