The Prognostic Value of Measuring PD-L1 mRNA Expression Levels in Surgically Resected Non-Small Cell Lung Cancer

Abstract

The expression of programmed cell death 1-ligand 1 (PD-L1) by tumor cells acts as an immune-checkpoint when it interacts with its receptor on immune cells, effectively preventing the immune system from attacking the tumor. Inhibitors against PD-L1 have shown remarkable therapeutic activity in non-small cell lung cancer (NSCLC); however, the prognostic value of this potential biomarker has yet to be conclusively shown. To investigate the clinicopathological and prognostic value of PD-L1 expression, we examined PD-L1 mRNA levels in surgically resected NSCLC. We compared PD-L1 mRNA expression in tumor and adjacent normal tissue from 71 NSCLC patient samples using real-time polymerase chain reaction. To validate PD-L1 mRNA expression by this method, PD-L1 protein expression by immunohistochemistry was analyzed and their strong correlation was confirmed (r=0.728, P=0.041). PD-L1 mRNA expression was significantly increased in tumor tissue as compared to adjacent normal tissue (P<0.001). Tumor tissue on average expressed 3.72 fold higher levels of PD L1 mRNA compared to normal tissue counterparts, and higher expression levels were found in 25.4% (18/71) of NSCLC samples. PD-L1 mRNA expression levels were not associated with clinicopathological characteristics of NSCLC. However, NSCLC patients with increased PD-L1 mRNA expression have a better prognosis than patients with low levels of PD-L1 mRNA (63.49 months vs. 98.53 months, χ2=3.73, p=0.053). Disease-free survival was 82.23 months and 45.68 months in patients with and without high levels of PD-L1 expression, respectively, although this difference was not significant (χ 2= 3.23, p=0.073). These results suggest that PD-L1 mRNA expression correlates to alterations in NSCLC disease progression; therefore, further comprehensive analyses should be performed.