The Expression Of BRD4 And ASCL1 And C-Myc Is Correlatied With The Prognostic In Small Cell Lung Cancer

Introduction: Lung cancer is the first leading cause of cancer-related deaths worldwide.Small cell lung cancer(SCLC)accounts for 15–20% of all lung cancers.Chemotherapy or chemotherapy plus chest radiotherapy is the standard treatment for SCLC,Although it is sensitive to initial treatment,and it is easy to relapse or resistance.Bromodomain protein 4(BRD4)regulates the expression of target genes by recruiting different transcriptional regulators.And it is a nuclear protein that binds to acetylated tails and plays an important role in maintaining chromatin architecture and controls transcription elongation.Different evidence supports the direct involvement of BRD4 in cancer.Recently,BET bromodomain inhibitors have shown antitumor activity in different preclinical models derived from hematologic or solid tumors.One study had reported MYC-specific inhibitory activity of a highly selective inhibitor of bromodomain and extra-terminal(BET)bromodomains,JQ1,in models of multiple myeloma and acute leukemia.However,the expression of BRD4 and ASCL1 and c-Myc has not been well studied for SCLC.Object : This study aimed to investigate the expression of BRD4,ASCL1 and C-Myc in small cell lung cancer,and analysis the correlation of the expression level of the those protiein corrected with prognosis in small cell lung cancer.To providing a potential therapeutic target of SCLC.Methods: Human small cell lung cancer tissues and matched para-cancerous lung tissues of 50 cases from the Affiliated Cancer Hospital of Xiangya School of Medicine,Central South University of thoracic surgery department and Lung Cancer and Gastroenterology Department.And it contains 10 pulmonary benign disease patients without tumor history.we performed the expression of BRD4 and ASCL1 and c-Myc in small cell lung cancer patients was measured by immunohistochemistry.Results: we found that the expression of BRD4 and ASCL1 and c-Myc in SCLC was 72% and 38% and12%,respectively.And they all staining was localized to the nucleus.And the expression of those protein in SCLC tissues was evidently stronger than that in their corresponding adjacent normal lung tissues and the difference was significant.And there have significant correlation between BRD4 and ASCL1,they both express the consistency of78%(p<0.05).Five-year overall survival(OS)(20% and 18%)and rates were significantly lower in the BRD4 and ASCL1 positive than in the BRD4 and ASCL1 negative groups(p<0.05)?Conclusions:we detected the BRD4,ASCL1,and c-myc have high levels of expression in the SCLC.with the consistency of BRD4 and ASCL1 being78%.The positive expression of BRD4 and ASCL1 was associated with the survival prognosis of patients with SCLC.