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  P2.06 - Poster Session 2 - Prognostic and Predictive Biomarkers (ID 165)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11581

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    P2.06-038 - Comparison of expression profiling of circulating and tissue miRNAs looking for possible non-invasive biomarkers for the treatment of metastatic NSCLC patients: preliminary results. (ID 2787)

    09:30 - 09:30  |  Author(s): K. Danza
    • Abstract

    Background
    Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Although some progress has been made in the development of its treatment, most patients are diagnosed at advanced stage and have a short overall survival rate. Just as specific genes have to be analyzed before selecting a targeted therapy, microRNAs (miRNAs) are emerging as biomarkers for NSCLC diagnosis and prognosis. miRNAs are small oligonucleotides that regulate target mRNAs in the post-transcriptional step driving the expression of some genes involved in the tumorigenesis of NSCLC. Due to their resistance to nuclease digestion, miRNAs can be detected both in lung tissue samples and in body fluids as circulating factors. Our aim was to identify specific non-invasive cancer biomarkers involved in NSCLC tumorigenesis regulation.

    Methods
    33 NSCLC patients, 19 male and 14 female, were enrolled. The mean age was 63.3 and 66% were smokers. 88% of patients had advanced stage (IIIb-IV) tumors of which 23 were adenocarcinoma and 10 squamous cell carcinoma. We collected serum before chemotherapy and, when available, tissue samples from biopsy. MiRNA expression profiling of 33 serum and 10 tissue paired samples and 10 serum samples from normal volunteers were investigated by Affymetrix GeneChip miRNA Array. meV software was used for statistical analysis, and target genes identified by deregulated miRNAs were analyzed through the miRWalk database.

    Results
    Statistical analysis revealed 47 miRNAs differentially expressed in NSCLC serum samples compared to control serum (p<0.05) and 29 miRNAs deregulated in NSCLC tissue samples compared to their normal counterparts. 326 miRNAs resulted differentially expressed between the serum and the tissue of NSCLC patients. Among these deregulated miRNAs, the Venn diagram comparing tumor/normal serum, tumor/normal tissue and tumor serum/tissue samples showed that the serum of NSCLC patients was characterized by 22 miRNAs, while 10 miRNAs identified the tumor tissue of NSCLC patients. Only one miRNA, miR-133a, was detected both in NSCLC serum samples and in tissue ones. Focusing on miRNAs involved in NSCLC pathogenesis, of 22 miRNAs miR-486-5p had a lower mean expression ratio (MER) in tumor vs normal serum (8.70±3.28 vs 10.78±1.35), as did let7b which had a MER of 5.28±2.63 in tumor serum vs 7.14±1.8 in normal serum samples. Of 10 miRNAs, miR-200c had the lowest MER in tumor vs normal tissue (1.25±0.10 vs 2.37±0.09 respectively) as did miR-29c* which had a MER of 2.18±0.08 in tumor tissue samples vs 2.34±0.11 in normal tissues. miR-133a had a comparable MER in tumor serum vs tumor tissue (2.41±0.17 vs 2.46±0.17 respectively). These miRNAs are able to target PIK3CA and PTEN genes, according to the miRWalk database, which are involved in the EGFR-related pathway.

    Conclusion
    Our results highlighted specific miRNA expression profiles, both in the serum and in the tissue of NSCLC patients, able to identify circulating miRNAs that could be used as non-invasive biomarkers for early diagnosis, or to predict prognosis in NSCLC patients thus improving personalized therapy. These data are preliminary to a prospective clinical validation in a multicentric trial.