Evaluation of miRNAs Levels of p53 Pathways in Non Small Cell Lung Cancer
J Ramirez, A Navarro, A Quera, T Diaz, A Huerta, N Vinolas, M Monzo, R Marrades. Hospital Clinic, IDIBAPS, CIBERES,Universitat de Barcelona, Barcelona, Spain; Facultat de Medicina. Universitat de Barcelona, Barcelona, Spain; Hospital Clinic. IDIBAPS, CIBERES, Barcelona, Spain
Background: The tumor suppressor gene p53 has been broadly studied in Non Small Cell Lung Cancer (NSCLC). It is found mutated in 55% of cases in NSCLC. MicroRNAs (miRNAs) are small RNA molecules that regulate mRNA translation to protein. Some miRNAs have been shown linked to p53 network. Protein p53 through his DNA binding domain activates the expression of miR-34 family in response to DNA damage or oncogenic stress, to induce apoptosis or cell cycle arrest. Recently, it has been described a novel p53 interaction through Drosha complex proteins, which allows p53 to regulate the maturation process of miR-16 and miR-143 to suppress cell proliferation.
Design: To explore the relationship between p53 mutation and miRNAs we have studied the clinical implications of miR-16 and miR-143 expression levels in 70 NSCLC patients and their relation to p53 mutations and miR-34a levels. It was possible to assess by sequencing p53 mutations in just 60 samples. We performed the same evaluation in normal tissue and in the tumor of all patients.We studied the expression of miR-16, 143 and 34a by real time PCR and analyzed data with SPSS 15.0.
Results: The data showed that miR-16 and miR-143 were downregulated in tumor tissues compared to normal tissues (p<0.001 and p=0.001 respectively). Concerning miR-16 expression, it emerged as an independent factor only for overall survival (OS) (RR=2.17; p=0.004). In the analysis that included miR-16 and p53 mutational status, both emerged as independent factors for disease free survival (DFS) (RR=1.9; p=0.024), but only mR-16 confirmed itself as an independent factor for overall survival. The analysis of miR-16 and miR-34 allow us to stratified three groups with different prognosis for DFS (p=0.002) and for OS (p<0.001) inside the patients that showed high miR-34a expression (good prognosis patients).
Conclusions: MicroRNA-16 appeared as a good marker for overall survival and seems to play a synergic role with miR-34a inside the p53 pathway. However, there is no relationship of their expression levels and p53 mutations in our set of patients. These miRNAs may be good targets for new therapeutics strategies in NSCLC. Supported by: FIS-PI060087 and FIS- PI040123; SEPAR; CIBERES.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 248, Tuesday Morning