P2.01-84 Serumal SERPINE2 as a Potential Biomarker for Radioresistance in NSCLC

Abstract

Radioresistance is the main reason for the failure of clinical radiotherapy in lung cancer. Among the different tumors, SERPINE2 is a protein with anticoagulant properties which could promote or inhibit solid tumor growth. However, its role in the pathogenesis of lung cancer has not been determined. To get radioresistant cell lines A549R and PC9R, A549 and PC9 cells were treated with fractionated irradiation by high energy X-ray. Cell survival fractions were measured by colony formation assay. Furthermore, we performed RNA-SEQ and protein profiling to screen genes differentially expressed in the A549/A549R and PC9/PC9R cells. To elucidate the biological role of SERPINE2 in radioresistance of NSCLC, we conducted SERPINE2 gene overexpression/knockdown experiments using NSCLC cell lines. The aim of this study was to assess serum SERPINE2 concentrations in a group of 26 NSCLC patients with radiation therapy alone in one course of treatment. Blood samples were collected before treatment. Serum SERPINE2 concentration was measured using specific ELISA methods. We analyzed its prognostic significance regarding outcome analysis, as well as its potential biomarker for radiotherapy. Two radioresistant lung adenocarcinoma sublines A549R and PC9R were successfully established through dose fractionated irradiation after six months. Results of RNA-SEQ and protein profiling showed the SERPINE2 was higher in A549R and PC9R compared to that in parental cells A549/PC9. We also demonstrated that knockdown of SERPINE2 expression inhibit cell migration and invasion in A549/PC9 cell lines. And the overexpression of SERPINE2 promote cell migration and invasion in H1975/HCC827 cell lines. Knockdown of SERPINE2 expression in the A549R/PC9R by shRNA also reduced significantly cell radiation resistance. The radiobiology parameters, which including SF2, D0, Dq and α/β, were significant differences compared with non-silencing shRNA cells. According to response evaluation criteria in solid tumors, the concentrations of SERPINE2 were significantly higher in PD patients compared with SD and PR. The preliminary study indicates the SERPINE2 play an important role in the radioresistance of NSCLC and implies the evaluation of SERPINE2 expression in serum may be considered as a potential biomarker in radiotherapy of NSCLC patients. Further research must be explored to clarify the function and mechanism of SERPINE2 in the radioresistance of lung cancer.