Abstract 1102P
Background
Blockade of programmed cell death protein-1 (PD1)/programmed cell death ligand-1 (PD-L1) interaction is one of important immunotherapies in lung cancers. Current research also focused on the relationship between genomic alterations and the expression of PD-L1. Therefore, we analyzed the molecular characteristics and its correlation with the expression of PD-L1, which may help to establish a reasonable tumor classification strategy to improve immunotherapy.
Methods
Tissue specimens were obtained from 391 cases suffered from lung cancer. Frequencies of gene alterations were detected and analyzed using next-generation sequencing(152 or 603 genes). All specimens were also performed for PD-L1 (22C3) by immunohistochemistry (IHC) with PD-L1 tumor proportion score (TPS) reported for further analysis.
Results
In 391 lung cancer samples, 113 (28.9%) cases had comutations in both TP53 and EGFR, 110 (28.1%) cases had alterations in EGFR only, 94 (24.0%) cases had alterations in TP53 only, and 74(18.9%) cases were wild-type of TP53 and EGFR. Two major alterated genes were TP53 (57.0%) and EGFR (52.9%), both of whose frequencies were significantly higher than the other tested genes (P < 0.05). Groups with alterations in EGFR, APC (3.3%) or RBM10 (4.1%) were significantly associated with the decreased expression of PD-L1 (P < 0.05), while alterations in TP53 were significantly associated with the increased expression of PD-L1 (P < 0.05).
Conclusions
Comparative analysis revealed that alterations (single or compound mutation) occured in either EGFR or TP53 affect the PD-L1 expression in this Chinese cohort. Although alterations in either EGFR or TP53 has independent and synergistic effects on the PD-L1 expression, there is limited evidence for those alterations serving as predictive biomarkers for the PD-L1 status. Furthermore, whether patients with both high PD-L1 expression and alterations in EGFR or TP53 can benefit from immunotherapies is still in question, and this subgroup is still worthy of clinical molecular recognition by further study.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Zhejiang Shaoxing Topgen Biomedical Technology Co. Ltd.
Funding
Zhejiang Shaoxing Topgen Biomedical Technology Co. Ltd.
Disclosure
All authors have declared no conflicts of interest.