NGS-Based Mutation Profiling and PD-L1 Expression in NSCLC Patients: A Single-Centre Prospective Analysis

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Non-small cell lung cancer (NSCLC) is characterized by molecular heterogeneity, impacting treatment decisions.
• Actionable mutations and programmed death-ligand 1 (PD-L1) expression are critical biomarkers for NSCLC therapy.
• Personalized medicine approaches require comprehensive molecular profiling.

Purpose of the Study:

• To evaluate the molecular profile of NSCLC using next-generation sequencing (NGS).
• To analyze the association between PD-L1 expression and key genetic alterations in NSCLC.
• To inform personalized therapeutic strategies by integrating molecular and immunophenotypic data.

Main Methods:

• Retrospective analysis of 87 histopathologically confirmed NSCLC cases.
• Molecular profiling using the Oncomine™ Lung Focus Assay for actionable mutations.
• PD-L1 expression assessment via immunohistochemistry (IHC) using Tumour Proportion Score (TPS).

Main Results:

• EGFR (36.2%), KRAS (16.2%), and AR amplification (14.3%) were the most frequent alterations.
• Actionable mutations were identified in 59.8% of patients, including EGFR, ALK, ERBB2, KRAS, MET, BRAF, and ROS1 alterations.
• PD-L1 expression (45.7%) was lower in EGFR-mutant tumors and higher in KRAS-mutant tumors, suggesting differential immunogenicity and potential predictive value for immunotherapy.

Conclusions:

• Integrating NGS-based molecular testing with PD-L1 evaluation is crucial for personalized NSCLC management.
• Distinct PD-L1 expression patterns across molecular subtypes (e.g., EGFR vs. KRAS mutations) necessitate tailored therapeutic strategies.
• Informed sequencing of targeted therapies and immunotherapies can be achieved through comprehensive molecular profiling.