Association of PD-L1 protein expression and TMB in non-small cell lung cancer.

Abstract

e20009 Background: Programmed death-ligand 1 (PD-L1) protein expression and tumor mutation burden (TMB) are considered to be two of the most promising biomarkers for predicting response to PD-1/PD-L1 blockade therapy. To evaluate the association of PD-L1 expression and TMB in non-small cell lung cancer (NSCLC), we designed a study to compare PD-L1 expression levels and TMB values from the same FFPE samples. Methods: 153 NSCLC patients were enrolled between August 2018 and January 2019. An FFPE sample with at least 10 sections was taken from each patient. DNA was extracted from half of the FFPE sections, and was sequenced using a 605 gene panel to 5,000× depth. In silico analysis was conducted to compare the TMB value obtained using this 605-gene panel with that determined using whole exome sequencing (WES). The Pearson rank correlation of TMBs determined using the 605 gene panel versus those using WES was 0.9379, indicating results of the two methods are highly consistent. The other halves of the FFPE sections were used to evaluate PD-L1 expression using immunohistochemical (IHC) techniques. Because WES is considered the gold standard for determining TMB, we re-analyzed WES sequencing data obtained from all 1049 NSCLC patient samples in the TCGA database, and demonstrated that the TMB determined using the 605 gene panel was highly consistent with that obtained using WES. Results: We determined that 22.22% (34/153) of samples had high PD-L1 expression (defined as > 50% of cells being PD-L1 positive), but their TMB values varied from 0.76 to 19.84. The correlation between PD-L1 expression and TMB was only 0.154, indicating that PD-L1 expression had no significant association with TMB. Conclusions: PD-L1 expression and TMB are both important biomarkers for PD-L1 therapy. Many patients were only tested for either PD-L1 expression or TMB due to cost and sample limitations. The results of our study suggest that both PD-L1 and TMB should be examined in NSCLC patients.