Condition category
Cancer
Date applied
02/05/2013
Date assigned
28/05/2013
Last edited
15/07/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Lay summary under review 3

Trial website

Contact information

Type

Scientific

Primary contact

Dr Francisco Gómez-Veiga

ORCID ID

Contact details

CHU A Coruña
Urology Service
C/Xubias de arriba 84
A Coruña
15006
Spain

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Analysis and quantification of microRNAs in prostate tumors: an observational study

Acronym

Study hypothesis

Cancer is essentially a genetic disease characterized by an uncontrolled proliferation and survival of damaged cells, resulting in tumor development. Prostate cancer is one of the main pathologies that must deal with the male population. In Europe we can state that it is the most common solid neoplasm followed by lung and colorectal cancer and the third leading cause of cancer death in men. We possess different predictive factors for this disease with the purpose to establish a prognosis and tailor the therapeutic strategies. However, the prognostic capacity of these parameters is limited and can be enhanced with the incorporation of other factors. In this sense, the miRNAs, small molecules that regulate various biological processes (division, differentiation, apoptosis, and metabolism) which have recently been involved in the development of cancer. Therefore, if the miRNAs are involved in oncogenesis, inflammatory response or other disease states, the expression studies of these RNAs of small size may reveal new diagnostic or prognostic markers.

Ethics approval

Ethics board: Clinical Research Ethics Committee of Galicia [Comité Ético de Investigación Clínica de Galicia (CEIC)], 29/03/2011

Study design

Observational study of cases and controls

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Prostate cancer

Intervention

1. Sample Collection: Peripheral blood samples will be collected into tubes containing EDTA with the sole precaution of discarding the first milliliters to avoid possible contamination of samples with epithelial cells which may subsequently interfere with the results.
2. Data collection and analysis: Data of usual clinical and prognostic variables (age, TNM-AJCC stage, location of primary sites of metastatic disease, hormone receptor status, degree of differentiation, etc.) will be collected at the time of inclusion of the patient, through a data collection form designed specifically for the study. Blood samples will be coded and specific data (volume obtained PCR results Real Time PCR, etc.) will be collected and analyzed separately from the clinical data. All variables will be stored in a computer database.
3. Finding differentially expressed miRNAs candidates: A computer support will be used in addition to the literature search on the website of the National Center for Biotechnology Information http://www.ncbi.nlm.nih.gov/entrez/query.fcgi) through free access databases of miRNAs on the following pages and others: http://mirnamap.mbc.nctu.edu.tw/;http://microrna.sanger.ac.uk/;http://www.ma.uniheidelberg.de/apps/zmf/argonaute/interface/. These pages are being updated constantly and are very useful for finding potential markers of miRNA (microRNA) that may be over-expressed or under-expressed in prostate tumors.
4. RNA extraction, PCR arrays, RT-PCR and real-time PCR (qRT-PCR): Once we get a panel of potential miRNA markers in blood of patients with prostate tumors, specific primers will be designed and to confirm the sensitivity of these studied its expression will be checked by RT-PCR in real time once the conditions are optimized for each microRNAs.
5. Biostatistical analysis of the results: The process of data normalization is essential for a correct process of quantifying the levels of microRNA here. Usually the method used in the standardization process is the use of a housekeeping gene. But in the case of miRNAs are still insufficient data which can be used as endogenous controls, so that expression data are normalized after selecting through the literature and verified by GENEX software (fine Analyser) those with more stable expression. The relative quantification of the expression of miRNAs will be calculated using the Genex software (fine Analyser) from the average log of expression of all the samples studied. The data will be analyzed using the viewer Multiexperiment programs TIGR version 4.6.1 (available in http://www.tm4.org/mev.html) and SPSS PASW Statistics 19. To identify miRNA with significantly different expression between different groups, multivariate analysis of permutations: Significance Analysis of Microarrays (SAM) with a False Discovery Rate <10%. The Analysis of Microarrays Prediction (MAP) will be used to identify those miRNAs that will be able to classify a sample into one group or another of those tested. Thus, by this analysis we will reduce the group of miRNA in importance according to the characteristics studied. The relationship between the positivity of the markers and clinical variables of interest will be studied using Chi-square test and logistic regression analysis in case of relative risks. The quantitative results will be compared using parametric statistics, unless the distribution of the variable results of studies advice the use of nonparametric statistics. Finally, we will conduct a study of time to progression and disease-free survival in such a way as to organize follow up patients for 5 years. We will make the relevant Kaplan Meier curves and to analyze their statistical significance log rank test will be used. Multivariate analysis will be performed using Cox's test, which will allow prognostic independence of the variables in study.

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

1. Look at the possible relationship between the expression profiles of the microRNAs and the ability of prediction groups risk in prostate cancer, in patients who have not suffered therapeutic maneuvers
2. Establish a panel of circulating microRNAs useful in the diagnosis and prognosis of prostate cancer

Secondary outcome measures

1. We will explore different patterns of microRNAs to estimate the response to the local therapy or hormonal manipulation including in the context of hormone-refractory patients
2. Identification of potential target genes of the microRNAs with significance by predictions of interaction through the mirbase database, TargetScan and the software's Crosslink and Pathway Studio (Ariadne Genomics)

Overall trial start date

29/03/2011

Overall trial end date

30/06/2015

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients with pathological diagnosis confirmed of localized, locally advanced or metastatic prostate cancer according to the TNM (tumor, lymph nodes, metastasis) classification, NCCN (National Comprehensive Cancer Network), during the period of study
2. Older than 18 years
3. Patients with signed informed consent

Participant type

Patient

Age group

Adult

Gender

Male

Target number of participants

81 prostate patients and 81 healthy volunteers

Participant exclusion criteria

1. Patients with a history of epithelial cancer, except skin carcinoma correctly treated
2. Patients who are receiving systemic cancer treatment
3. Thrombocytopenia less than 20,000 /ml or coagulopathies not medically controlled

Recruitment start date

29/03/2011

Recruitment end date

30/06/2015

Locations

Countries of recruitment

Spain

Trial participating centre

CHU A Coruña
A Coruña
15006
Spain

Sponsor information

Organisation

The Foundation for Research in Urology [Fundación para la Investigación en Urología (FIU)] (Spain)

Sponsor details

C/Valenzuela 6
1*Derecha
Madrid
28014
Spain

Sponsor type

Charity

Website

http://www.aeu.es

Funders

Funder type

Charity

Funder name

The Foundation for Research in Urology (Beca Fundación para la Investigación en Urología) (Spain) 2010-2012

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. Circulating miR-337-3p as a novel biomarker for prostate cancer. Manuel Valladares Ayerbes1, Vanessa Medina Villaamil2, Sara Martinez Breijo3, Isabel Santamarina Cainzos2, Guadalupe Aparicio2, Jose Gonzalez Dacal3, Paula Portela Pereira3, Dario
Vazquez Pazos3, Francisco Gomez-Veiga3, Luis M. Antón Aparicio1, 4. 1-Medical Oncology Service, Complejo Hospitalario Universitario A Coruña, A Coruña, Spain; 2-Biomedical Research Institute, A Coruña, Spain; 3-Urology Service, CHU A Coruña, A Coruña, Spain; 4-Medical Department, UDC, A Coruña, Spain. Accepted as Poster presentation for the 2013 ASCO Annual Meeting (May 31 - June 4, 2013)
2. MicroRNAs as emerging biomarkers for micrometastasis detection in prostate tumors. Francisco Gómez Veiga1, Vanessa Medina Villaamil2, Sara Martínez Breijo1, Isabel Santamarina Cainzos2, Jose González Dacal1, Paula Portela Pereira2, Darío Vázquez Pazos1, María Quindós Varela3, Manuel Valladares Ayerbes3, Luis Antón Aparicio3, 4. 1-Urology Service, CHU A Coruña, A Coruña, Spain; 2- Biomedical Research Institute, A Coruña, Spain; 3- Medical Oncology Service, Complejo Hospitalario Universitario A Coruña, A Coruña, Spain; 4- Medical Department, UDC, A Coruña, Spain. Accepted as Poster presentation for AUA 2013, (San Diego, May 2013)
3. The microRNA profile of prostate carcinoma risk groups obtained by SYBR-green-based miARN RT-qPCR arrays.V Medina Villaamil, S Martínez Breijo, F Gómez Veiga, J Ponce Díaz-Reixa, JA González Dacal, V Chantada Abal, I Santamarina Caínzos, G Aparicio Gallego, LM Antón Aparicio. Presented as Poster at Systems Biology, Select Biosciences. Madrid, Spain. October 2012
4. Papel de los microARNs como biomarcadores de detección de micrometástasis en tumores de próstata. Martínez Breijo, S; Medina Villaamil, V; Ponce Díaz-Reixa, J; Gonzalez Dacal, J; Santamarina Cainzos, I; Blanco Castro, E; Pertega, S; Casas Nebra, J; Zarraonandía Andraca, A; Antón Aparicio, L; Gómez Veiga, F; Chanatada Abal, V. Presented as Poster at LXXVII Congreso Nacional de Urología. Vigo, Spain. June 2012.
5. Análisis de microARNs circulantes como biomarcadores de detección de micrometástasis en tumores de próstata. Martínez Breijo, S; Medina Villaamil, V; Ponce Díaz-Reixa, J; González Dacal, J; Santamarina Caínzos, I; Portela Pereira, P; Blanco Castro,
E; Pertega, S; Casas Nebra, J; Zarraonandía Andraca, A; Antón Aparicio, L; Gómez Veiga, F; Chantada Abal, V. Presented as Oral comunication at XXII Congreso de la Sociedad Gallega de Urología. Lugo, Spain. May 2012

Publication citations

Additional files

Editorial Notes