Prognostic microRNA Signature in Early Stage Lung Adenorcarcinomas (ADK): Preliminary Results
C Ortholan, V Hofman, C Bonnetaud, O Bordonne, M Ilie, V Virolle, T Virolle, N Venissac, J Mouroux, P Barbry, B Mari, P Hofman. CHU, Nice, France; INSERM, Nice, France; CNRS UMR6097, Nice, France
Background: 20% of stage I Non Small Cell Lung Carcinomas (NSCLC) relapse within 2 years after surgery. Therefore, the identification of biologic prognostic factors of early stage NSCLC is relevant. The clinical significance of miRNAs signature in early stage NSCLC remains unclear. The purpose of this study was to evaluate the prognostic value of microRNAs in patients with stage I ADK.
Design: Crieteria of eligibility were T1-T2N0 primary lung ADK treated with surgery between 2005 and 2007. Nine patients presented local or metastatic recurrence (= group 1). Each of these patients were matched with 2 patients without any recurrence (= group 2), according to the following criteria : tumor size, pleural involvment, adjuvant chemotherapy, % of tumor cell within the tumor sample, TTF-1 status. MicroRNA microarray expression profiling of tumors and paired nontumorous tissues was performed on these 27specimen.Total RNAs were extracted with TRIzol solution from frozen sample. MicroRNAs were purified on column with the Mirvana kit and chemically labelled with Alexa Fluors. Labelled-miRNA hybridized on microChip containing 2054 probes, including the whole human microRNome. The expression of each microRNA was quantified in tumor and corresponding healthy tissue. Disease-free survival (DSF) was defined with the Kaplan-Meier method.
Results: Tumor samples had a specific microRNA signature compared with healthy tissue(such as down regulation of mir-126, mir-30, let 7, mir-145, up regulation of mir-21 and mir –35). A hierarchical clustering was performed in 35 selected microRNA.When comparing levels of expression of microRNA between group 1 and 2, 4 microRNAs were significantly associated with cancer recurrence : up regulation of mir-21, mir-297, and downregulation of mir-30a and mir-99a, consisting in a specific microRNA signature.Two-years DFS was 33% in patients with the specific Micro-RNA S signature (MRS) vs 89% for the others (p<0.0001). In this set of patients, sensitivity and specificity of the specific MRS for disease rcurrence was 78% and 89%, respectively.
Conclusions: This study is the first to demonstrate that a specific MRS of early stage lung ADK could predict the risk of cancer recurrence. These results are under validation in a multicentric independant cohort of stage I lung adenocarcinomas in order to transfert these findings in clinical practice.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 249, Tuesday Morning