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J. Cao



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    O01 - Prognostic and Predictive Biomarkers I (ID 94)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      O01.02 - MicroRNA Signature Predicts Survival in Resectable Small-Cell Lung Cancer (ID 1641)

      10:40 - 10:50  |  Author(s): J. Cao

      • Abstract
      • Slides

      Background
      Small-cell lung cancer (SCLC) is one of the most aggressive types of cancer, yet the molecular mechanisms underlying its devastating clinic outcome remain elusive. In this study, we investigated whether microRNA (miRNA) expression profiles can predict clinical outcomes of SCLC patients.

      Methods
      A total of 82 patients with very limited SCLC, who received surgical resection followed by adjuvant chemotherapy according to the standard of care, were enrolled in this study. All the tumor samples used for miRNA profiling were required to contain at least 60% tumor cells and RNA was isolated from formalin-fixed paraffin-embedded specimens. First, we surveyed 924 miRNAs for their expressions from 42 SCLC patients to discover survival relevant miRNAs and develop prognostic models, which were then validated in an independent cohort of 40 cases. A risk score of miRNA signature for survival prediction was calculated according to a combination of expression level of the miRNA weighted by the regression coefficient derived by univariate Cox regression analysis. Kaplan-Meier overall survival curves were compared using the log-rank test and multivariate Cox regression model was used to test if the miRNA signature was an independent prognostic factor.

      Results
      For all the patients, the median follow up time was 57.2 months. Forty-four patients (53.7%) are still alive. Forty-two patients (51.2%) had recurrent disease and the median time to diagnosis of relapse was 12.3 months. In the training set, we identified that two miRNAs, miR-150 and miR-886-3p, were significantly associated with poor OS. The results compared between NL and SCLC tissues also verified that the miR-150 and miR-886-3p expression levels in SCLC were much lower than in normal lung samples (884±126 vs 2954±1652 for miR-150 and 1873±256 vs 3154±448 for miR-150 ). We then derived a miRNA signature 0.545×miR-150 + 0.617 ×miR-886-3p. Compared with patients with low-risk miRNA signature, patients with high-risk signature had significantly shorter median OS (12.6 months versus not reached, P=0.02). This signature was also demonstrated to be a significant predictor of survival in the validation set. Patients with high risk miRNA signatures had poor overall survival (P=0.005) and progression-free survival (P=0.017) compared to those with low-risk scores. It retained statistical significance in a model adjusting for age, gender and smoking status (HR 0.27, 95% CI 0.10-0.72, P=0.008), which suggesting that the miRNA signature may be an independent predictor of survival.

      Conclusion
      In this study, we developed a prognostic miR-150/miR-886-3p signature and validated in an independent dataset for resectable SCLC. Our results indicated that microRNAs may serve as promising molecular prognostic markers as well as new therapeutic targets for SCLC. Larger sample size studies are needed to further validate our findings.

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