Peripheral Blood Glucocorticoid Receptor α/β (GRα/GRβ) Ratio Predicts Response to Pemetrexed-Based Chemotherapy in Non-Squamous NSCLC: A Prospective Cohort Study.

Background: This study evaluated whether the glucocorticoid receptor α/β (GRα/GRβ) mRNA expression ratio in peripheral blood mononuclear cells (PBMCs) can serve as a predictive biomarker for treatment response and survival in patients with non-squamous non-small cell lung cancer (NSCLC) receiving pemetrexed-based chemotherapy. Methods: Thirty-five patients with confirmed non-squamous NSCLC were prospectively enrolled and received platinum-pemetrexed chemotherapy with standard dexamethasone premedication. Quantitative PCR was used to measure GRα and GRβ mRNA levels in PBMCs, and patients were categorized into high- and low-ratio groups based on the median GRα/GRβ value. Tumor response was assessed per RECIST 1.1 criteria, and progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier and Cox regression methods. Results: Compared with the high-ratio group, patients in the low GRα/GRβ group had a higher response rate (82.4% vs 44.4%, Conclusion: A lower GRα/GRβ ratio in PBMCs was suggestively associated with improved tumor response and PFS in this small, exploratory cohort. However, the limited sample size, lack of an independent validation cohort, reliance on PBMC-derived measurements, potential confounding factors, and absence of multiple comparisons adjustment warrant cautious interpretation. These results should be considered hypothesis-generating, and validation in larger, multicenter, and adequately powered studies-including paired PBMC-tumor analyses-is essential before clinical implementation.