PD-L1 and c-MET expression and survival in patients with small cell lung cancer.

Lulu Miao,Yanjun Xu,Zhiyu Huang,Gu Zhang,Yunyun Lu,Yun Fan,Lei Gong

doi:10.18632/oncotarget.9765

Abstract

BackgroundBlocking the binding between the PD-1 and PD-L1 has been reported to produce antitumor responses. The MET/HGF axis appears to be another signaling pathway frequently altered in small cell lung cancer (SCLC). Our study was aimed to investigate the expression and prognostic roles of PD-L1 and c-MET in SCLC.MethodsThe expression levels of PD-L1 and c-MET were evaluated by immunohistochemical analysis in 83 SCLC specimens. Survival analysis was performed using the Kaplan-Meier method.ResultsOf the SCLC specimens, 51.8% and 25.3% exhibited positivity for PD-L1 and c-MET, respectively. Higher PD-L1 expression in tumor specimens was significantly correlated with a limited disease (LD) stage, normal levels of serum lactate dehydrogenase (LDH) and neuron-specific enolase (NSE). No association was found between the levels of c-MET and PD-L1 expression or between c-MET expression and other clinical characteristics. SCLC patients with PD-L1-positive tumors showed significantly longer overall survival (OS) than patients with PD-L1-negative tumors (17.0 vs 9.0, p=0.018). Conversely, those with positive c-MET expression exhibited a shorter OS trend (12.0 vs 15.0, p=0.186). However, sub-analysis of LD-stage patients revealed longer OS among the c-MET-negative group (25.0 vs 14.0; p=0.011). The OS of patients with positivity for both PD-L1 and c-MET showed no significant difference compared with other patients (p=0.17). According to multivariate analyses, neither PD-L1 nor c-MET immunoreactivity was a prognostic factor.ConclusionExpression of PD-L1 was correlated with LD stage and might serve as a prognostic for better OS in SCLC patients. In LD-stage patients, high c-MET expression might be predictive of a poor outcome.

Highlights

Small cell lung cancer (SCLC), which accounts for approximately 13-15% of all primary lung cancers [1], is one of the most aggressive types of lung cancer
Higher programmed death– ligand 1 (PD-L1) expression in tumor specimens was significantly correlated with a limited disease (LD) stage, normal levels of serum lactate dehydrogenase (LDH) and neuron-specific enolase (NSE)
No association was found between the levels of c-Mesenchymal-epithelial transition (MET) and PD-L1 expression or between c-MET expression and other clinical characteristics

Summary

Introduction

Small cell lung cancer (SCLC), which accounts for approximately 13-15% of all primary lung cancers [1], is one of the most aggressive types of lung cancer. 60%-70% of SCLC patients are staged at the ED stage at the time of diagnosis [2]. For ED patients, the mOS is 8–13 months, with a dismal two-year survival rate of approximately 5% [3]. Despite rapid progress in our knowledge of the molecular biology of non-small cell lung cancer (NCSLC) and the development of targeted therapy, www.impactjournals.com/oncotarget conventional chemo- and radiation therapy for SCLC over the last few decades has remained largely unchanged [4]. The MET/HGF axis appears to be another signaling pathway frequently altered in small cell lung cancer (SCLC). Our study was aimed to investigate the expression and prognostic roles of PD-L1 and c-MET in SCLC

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Conclusion