Abstract 3713: Strong expression of EZH2 and H3K27me3 is associated with poor survival time in small cell lung cancer

Abstract

Abstract BACKGROUND: Small-cell lung cancer (SCLC) is a highly aggressive neoplasm, characterized by early development of metastasis and very poor clinical outcome. The therapeutic possibilities are limited and poorly changed over the past three decades. Enhancer of zeste homolog 2 (EZH2) is a member of the polycomb repressive complex 2. It is involved in epigenetic gene silencing through the trimethylation of H3K27 and it has been identified as a biomarker of aggressive and highly proliferating tumors, emerging as a potential target for cancer therapy. OBJECTIVE: We aimed to correlate the expression profile of the EZH2 and H3K27me3 proteins in tumor tissues of non-treated SCLC patients with patient's outcome. METHODS: EZH2 and H3K27me3 expression were analyzed by immunohistochemistry in 48 SCLC tumor biopsies. The expression of the markers was quantified in a semi quantitative way and correlated with clinic pathological factors and patients overall survival. To mimic an EZH2 loss, H209 SCLC cells were treated with an EZH2 inhibitor for 48h and the in vivo growth pattern was investigated in the chorioallantoic membrane (CAM) assay. RESULTS: All patients died within one year after diagnosis. There was a heterogeneous expression pattern for EZH2 and H3K27me3. Strong expression of EZH2 and H3K27me3 was observed in appr. 50% of the patients. The Kaplan Meier curve showed a significant association of high expression pattern of EZH2 and shorter overall patient survival time after 12 and 25 weeks of follow up, respectively (p=0.030; p=0.014) Different markers of tumor aggressiveness after EZH2 inhibition were investigated in the CAM model. CONCLUSION: Strong EZH2 and H3K27me3 expression in non-treated SCLC patients was related to worse prognosis. EZH2 inhibitors should be considered in future trials for SCLC. Citation Format: Ana Paula Fernandes, Rita deCassia S Alves, Guilherme Watte, Philipp Kunze, Adriana Vial Roehe, Regine Schneider-Stock. Strong expression of EZH2 and H3K27me3 is associated with poor survival time in small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3713.