EP1.12-22 The Expression and Prognostic Roles of PD-L1, PAPR1 and DLL3 in Small Cell Lung Cancer

Abstract

Small cell lung cancer (SCLC) is an aggressive high-grade neuroendocrine tumor with limited treatment. Recently chemotherapy combined with anti-PD-L1 therapy was approved for SCLC. PARP1and DLL3 inhibitor are under clinical trials but the data revealed that these agents benefit a proportion of SCLC patients. Which patient can benefit from anti-PD-L1, PARP1 and DLL3 inhibitor therapy and whether combination of these agents can improve the survival of SCLC are unknown. We aim to examine the expression and prognostic roles of PD-L1, PARP1 and DLL3 and to analyze the correlation between them and clinicalpathological factors. All protocols were approved by the Ethics Committee of Xi'an Jiaotong University and informed consent was signed. FFPE samples were obtained from Department of Pathology at The First Affiliated Hospital of Xi'an Jiaotong University from 2011 to 2018. SCLC was confirmed in all patients by surgical pathology and graded by AJCC TNM staging system. The expression of PD-L1, PARP1 and DLL3 were detected by immunohistochemistry as previously described. The association between PD-L1, PARP1, DLL3 and clinicalpathological characteristics was performed by χ2 test. The survival curves were analyzed by the log-rank test and Cox proportional hazards model. Except for CYFRA21-1 and DLL3, no correlation between PD-L1, PARP1 and DLL3 and clinicalpathological factors were noticed (Table 1).Table 1Correaltion between PD-L1, PARP1, DLL3 and clinialpathological factors in SCLC patientsPD-L1 negativePD-L1 positiveχ2PPARP1 negativePARP1 positiveχ2PDLL3 negativeDLL3 positiveχ2PAge<601112176815>=608130.420.561730.800.747110.070.79GenderMale14212871528Female440.270.70620.101.00350.101.00Smoking statusSmoker (including previous smoker)12152341017Never-smoker6100.200.761151.640.265110.150.70Central or PeripheralCentral11162161017Peripheral790.041.001330.071.005110.150.70CEA levelCEA normal912165714CEA high4479247Unknown925.680.06920.130.90470.040.98CYFRA21-1 levelCYFRA21-1 normal711144513CYFRA21-1 high579393Unknown670.160.921120.030.83497.540.02NSE levelNSE normal201102NSE high10172161116Unknown683.040.221220.790.494101.730.42TNM stageTNM stage 1-210131310617TNM stage 3-47120.190.661633.730.059111.690.19 Open table in a new tab We also demonstrated that PD-L1 predicts poor prognosis (HR=0.26, P=0.01), while either PARP1 or DLL3 has no correaltion with prognosis in SCLC patients (HR=0.40, P=1.39 and HR=0.07, P=1.29 respectively). Interestingly, we found SCLC patients with negative PD-L1 and PARP1, negative PD-L1 and DLL3 performed the best survival (Figure 1). PD-L1 is a negative prognositc factor in SCLC. Different expression pattern of PD-L1 and PARP1, PD-L1 and DLL3 lead to significantly different prognosis in SCLC.