Micro RNA Profile of High Grade Prostate Carcinoma
KRM Leite, JM Sousa-Canavez, ST Reis, LH Camara-Lopes, M Srougi. University of Sao Paulo Medical School, Sao Paulo, Brazil; Genoa Biotechnology, Sao Paulo, Brazil
Background: Although incidental prostate cancer (PCa) has been reported in up to 80% of autopsies, only a small percentage of men will die from the disease. There is a biological continuum from an indolent tumor to a highly aggressive and potentially fatal form. Treatment options are variable from active monitoring to palliative androgen-ablation. PSA, Gleason score and clinical stage are the main prognostic factors, but there is an urgent need for new molecular markers to be applied in the identification of unfavorable disease. MicroRNAs (miRNAs) are small (2022 nucleotides) regulatory RNAs that complementary binding to mRNA sequences repress target-gene expression. A large number of miRNAs has been related to the development of neoplasias, and are denominated oncomirs. The aim of our study is to determine a profile of miRNA related to high grade PCa that could be used as prognostic marker for therapeutic decisions.
Design: Nineteen patients underwent radical prostatectomy for treatment of localized high grade PCa. The mean age was 64.4 years old, mean Gleason score 8.6, and mean tumor volume 11.6 cc. Eighteen were staged pT3N0 and one pT3N1. Fourteen miRNA were studied by quantitative real time PCR. The specimens of six retropubic prostatectomies for treatment of benign prostate hyperplasia were used as control. The endogen control was 2-microglobulin.
Results: The results are in figure 1. The majority of miRNA was shown to be overexpressed. mi-218, mi-let7 and mi-100 were overexpressed in 18 from 19 cases (94.7%) and mi-25 was overexpressed in 17 from 19 (89.5%). mi-Let7 has been called as a tumor suppressor miRNA since it regulates negatively the expression of Ras and c-Myc, the later related to PCa aggressiveness. But conversely we found it overexpressed by almost 95% of our cases.
Conclusions: Each miRNA has around 100 genes targets, and their expression is tissue specific. The meaning of specific profiles of miRNA in human tumors is only beginning to be understanding and more studies with large series have to be conducted in order to turn this information useful in the clinical practice.
Category: Special Category for 2009 - Pan-genomic/Pan-proteomic approaches to Cancer
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 235, Tuesday Morning