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E. Nadal



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    MINI 34 - RNA and miRNA (ID 162)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      MINI34.03 - Novel microRNA Prognostic Signature in Malignant Pleural Mesothelioma (ID 2988)

      18:40 - 18:45  |  Author(s): E. Nadal

      • Abstract
      • Presentation
      • Slides

      Background:
      Malignant pleural mesothelioma (MPM) is an aggressive tumor mainly associated with asbestos exposure. MPM patients have a poor outcome (median overall survival (mOS) <1 year), therefore novel therapeutic approaches are needed. MiRNA have been demonstrated to have a role in tumorigenesis and progression in MPM. This study aimed to identify a miRNA signature associated with poor prognosis.

      Methods:
      We identified 26 un-resected MPM patients split as follows: 11 long survivors (LS) OS>3 years and 15 short survivors (SS) OS<1 year. MiRNA expression in 26 FFPE biopsy and 3 normal pleura (NP) was evaluated using Agilent Human miRNA Microarray platform including 2006 miRNA. Expression data were normalized by GeneSpring software (v.12.6). Class-comparison analysis between MPM/NP and SS/LS was performed using a t-test adjusted for multiple comparisons using Benjamini-Hochberg. OS curves were estimated using the Kaplan-Meier method and compared with the log-rank test. In silico validation was performed using miRseq data from TCGA portal based upon 16 patients (LS: 8; SS: 8). Candidate miRNA were assessed by univariate analysis using Kaplan-Meier method and median as cutoff.

      Results:
      Patients’ characteristics: median age 67 years (53-77); 81% males, 19% females; 73% epithelioid histotype, 12% sarcomatoid, 12% biphasic and 1 unspecified MPM. No differences in age, gender and histotype were observed between LS and SS. By class-comparison analysis, 30 miRNAs were significantly up-regulated and 11 down-regulated in MPM vs NP (adjusted p-value <0.05). Fourteen miRNAs were significantly associated with outcome, in the univariate survival analysis and differentially expressed in MPM. A miRNA signature, based on the top 6 prognostic miRNAs (unfavorable, miR-1224; favorable, miR-99a, miR-125b, let-7b, let-7c and let-7i) classified patients into low- or high-risk. High-risk patients showed a significantly shorter median OS (4.1 months, 95% CI 2.2-5.9) as compared with low-risk patients (median not reached, Log-rank p<0.001). In silico validation analysis confirmed that low expression of mir-99a, miR-125b and let-7c was associated with shorter OS. Relevant pathways, such as PI3K/AKT, WNT were associated with these top miRNAs by pathway analysis.

      Conclusion:
      A prognostic miRNA signature was identified by profiling a cohort of un-resected MPM, underlying the clinical potential of miRNA as predictors of survival. An additional validation in a larger independent cohort of MPM is ongoing.

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