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Flavia Centra



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    P2.14 - Targeted Therapy (ID 183)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.14-32 - Epigenetic Silencing of SPARC in NSCLCs (ID 2345)

      10:15 - 18:15  |  Author(s): Flavia Centra

      • Abstract

      Background

      The silencing of SPARC gene through methylation of its promoter region has been commonly observed in many solid tumors and is frequently associated with tumor progression and an aggressive clinical outcome. At present, the data concerning the mechanisms of SPARC deregulation in lung cancer are almost incomplete and correlation analysis with disease clinical course and specific therapeutic strategies is ongoing. Here we present the epigenetic profile of SPARC gene promoter in a collection of NSCLC cell lines and tissue samples and assess its prognostic value in surgical NSCLC resected patients.

      Method

      Four cell lines (3 adenocarcinoma, ADC and 1 large cell carcinoma, LCC) and 66 primary NSCLC tissues from surgically resected patients (30 squamous cell carcinoma, SqCC and 36 ADC) and 11 lung non-neoplastic tissues were epigenetically scanned. Promoter methylation analysis was performed using a quantitative methylation specific PCR assay in real-time (QMSP). The downstream effect of epigenetic silencing was also investigated in A549 and H1573 NSCLC cell lines by 5-Aza-2’-deoxycytidine treatment to demonstrate if the demethylating agent was able to restore SPARC mRNA expression levels. SPARC methylation levels were correlated with clinicopathological features.

      Result

      A tumor-specific DNA methylation of the SPARC gene promoter region was found as a specific feature of NSCLC (p=00643 Mann-Whitney test) and was also observed in all cell lines analyzed. In particular, it was detected in 56% of SqCCs (20/36) and 64% of ADCs (19/30), with SqCC showing the highest levels of methylation. Overall, we found promoter hypermethylation in 59% of NSCLCs. Moreover, a direct correlation with mRNA levels was confirmed by in vitro 5-azacytidine treatment. In SqCCs, SPARC methylation levels correlated with a negative prognosis (p<0,012 Supremum Test for Functional Form, HR=1,93; 95%CI).

      Conclusion

      Our results further suggest that epigenetic deregulation of the SPARC gene could be involved in the cancerogenesis of NSCLC. Additional studies on a larger cohort of NSCLCs and correlation with clinic-pathological features may contribute to disease progression prediction and new molecular basis to codify the response to therapy in lung cancer patients.