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C. Leygo



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    P1.09 - Mesothelioma (ID 695)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Mesothelioma
    • Presentations: 1
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      P1.09-008 - A 4-microRNA Signature in Serum Can Discriminate Between Non-Small-Cell Lung Cancer and Malignant Pleural Mesothelioma (ID 9956)

      09:30 - 09:30  |  Author(s): C. Leygo

      • Abstract
      • Slides

      Background:
      Differential diagnosis of malignant pleural mesothelioma (MPM) and non-small cell lung cancer (NSCLC) can be difficult. For both malignancies various studies have in recent years investigated circulating cell-free microRNAs (miRs) as potential diagnostic markers, with most of these focusing on NSCLC. One of the most recent studies has suggested a 4-miR signature consisting of miR-141, miR-200b, miR-193b and miR-301 in serum to be specific for NSCLC patients. Here, we investigated the value of this 4-miR signature in discriminating serum samples from NSCLC and MPM patients.

      Method:
      RNA was extracted from a series of serum samples from 98 NSCLC, 98 MPM and 96 healthy controls collected at the Netherlands Cancer Institute between 1995 and 2011. MicroRNA-specific TaqMan assays were used to quantify serum microRNA levels in the t groups which after initial quality control consisted of 65, 68 and 58 samples in the NSCLC, MPM and control groups, respectively. Expression levels of individual microRNAs between the different groups were analysed using one-way ANOVA with Tukey-Kramer Posthoc Test. Binary logistic regression modelling was used to generate the 4-miR-signature, for which accuracy in discriminating NSCLC from MPM or healthy was analysed by ROC curve analysis.

      Result:
      Analysis of the signature microRNAs showed for all 4 miRs trends towards higher abundance in serum from NSCLC patients. Statistical significance was however only reached for miR-141, which was found to be increased by 4.4-fold in NSCLC compared to healthy controls (p=0.014) and by 5.6-fold in NSCLC vs MPM (p=0.004). Although we did not observe significant differences in abundance for all microRNAs, ROC curve analysis of the 4-miR signature confirmed the discriminatory potential with an AUC 0.73 (95% CI: 0.62-0.85) for NSCLC vs healthy controls. When applying the best achievable Youden Index as cut-off point, the signature showed a sensitivity of 91.4% and a specificity of 44.4%. In addition to being able to discriminate NSCLC from healthy controls, the 4-miR-signature also proved to be valuable for discriminating NSCLC from MPM, where an AUC of 0.77 (95% CI: 0.66-0.89), a sensitivity of 74.3% and a specificity of 80.4% could be observed.

      Conclusion:
      Initial analyses have confirmed the diagnostic potential of the previously described NSCLC-specific serum-based microRNA signature for distinguishing NSCLC from healthy controls. In addition, we have shown that the same signature can also discriminate between NSCLC and MPM.

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