WCLC 2025 - Posters & ePosters-P2.06.52 Survival and Mutational Differences of GPER and Estrogen Receptor (ER) in NSCLC

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This study investigates the roles of G-protein coupled estrogen receptor 1 (GPER) and estrogen receptors alpha (ESR1) and beta (ESR2) RNA expression in non-small cell lung cancer (NSCLC) survival and mutational profiles. Analyzing 52,690 NSCLC samples via next-generation sequencing, researchers found that GPER expression correlates positively but weakly with ESR1 (r=0.384) and ESR2 (r=0.424). Higher GPER expression (GPER-H) was more prevalent among females (51.1% vs. 47.7%) and associated with increased EGFR mutations but decreased mutations in STK11 and KEAP1 compared to low GPER expression (GPER-L). No significant differences were observed in BRAF, KRAS, NRAS, or HRAS mutations by GPER status.<br /><br />Survival analysis revealed that elevated ESR1 and ESR2 expression correlates with longer median overall survival (mOS), whereas high GPER expression associates with shorter mOS overall and stratified by sex. Specifically, in females with ESR1-H tumors, GPER-H predicts worse survival; in males with ESR1-H tumors, this effect is not seen. For ESR2-H tumors, GPER-H correlates with worse survival in both sexes, albeit with smaller differences in males. Adjusted analyses confirmed that GPER-H independently predicts shorter mOS in ESR1-L (adjusted hazard ratio [aHR] 1.21, p=0.02) and ESR2-L (aHR 1.33, p=3.84E-4) tumors, controlling for histology, gender, and key driver mutations.<br /><br />These findings indicate that GPER interacts distinctly with ESR1 and ESR2, influencing mutational landscapes and survival outcomes in NSCLC, particularly in female and EGFR-mutant patients. The data suggest that therapeutic targeting of both GPER and estrogen receptors may improve survival in these populations.

Asset Subtitle

Robert Hsu

Meta Tag

Speaker Robert Hsu

Topic Pathology and Biomarkers

Keywords

GPER

ESR1

ESR2

non-small cell lung cancer

NSCLC

EGFR mutations

survival analysis

RNA expression

sex differences

mutational profiles