PD-L1 Expression and Comprehensive Molecular Profiling Predict Survival in Nonsmall Cell Lung Cancer: A Real-World Study of a Large Chinese Cohort

Abstract

Background: Programmed death ligand 1 (PD-L1) expression is the current standard biomarker used to predict non-smallcell lung cancer (NSCLC) response to immunotherapy. Gene expression signatures also seem to be related to the response to immunotherapy. Understanding the clinical and prognostic impact of molecular phenotype and tumor features on PD-L1 expression in NSCLC patients may improve the prediction of immunotherapy response.

Materials and methods: A total of 819 consecutive surgically resected NSCLC specimens from one institution were analyzed in our study. We determined PD-L1 expression by immunohistochemistry (IHC) using the 22C3 clone and the molecular phenotype by targeted next-generation sequencing with a 68-gene panel.

Results: High PD-L1 expression was significantly associated with wild-type EGFR (P < .001), KRAS mutation (P < .001), ROS1 rearrangement (P < .001), ALK rearrangement (P = .007), RET rearrangement (P = .041) and MET gene alterations (P = .003). Mutations in TP53 and Rb1 were also significantly associated with high PD-L1 expression (both P < .001). High PD-L1 expression was significantly associated with EGFR co-mutation with tumor suppressor genes such as TP53, Rb1, while EGFR mutation alone was not associated with high PD-L1 expression. Poor survival appeared to be linked to high PD-L1 expression or PD-L1 negative expression with concomitant mutations of tumor suppressor genes, especially multiple tumor suppressor genes.

Conclusion: PD-L1 expression is highly correlated with major driver and suppressor gene alterations. High PD-L1 expression and patients with negative PD-L1 expression harboring suppressor gene mutation are associated with poor prognosis in patients with NSCLC.

Keywords: Lung tumor; Molecular alterations; Predict value; Programmed death ligand 1.