2024 World Conference on Lung Cancer (WCLC) - Posters-P1.06B.02 A Comprehensive Analysis of FGF/FGFR Signaling Alteration in NSCLC

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The study comprehensively analyzes fibroblast growth factor (FGF) and fibroblast growth factor receptor (FGFR) signaling alterations in non-small cell lung cancer (NSCLC). FGF and FGFR modifications are recognized as critical targets in NSCLC treatment but are not yet fully understood in terms of survival, clinicopathological significance, and the tumor microenvironment. Using next-generation sequencing, 4,656 NSCLC cases were examined, identifying 478 cases with FGF/FGFR alterations. The analysis aimed to provide evidence-based insights into these signaling changes.<br /><br />Key findings include that FGF pathogenic variants (PV) and FGF/FGFR/KRAS combinations are independent factors negatively affecting prognosis. Co-mutation with the KRAS gene in the FGF/FGFR context is particularly associated with a poor prognosis. Furthermore, certain variant combinations, such as NOTCH1 with FGFR1 or RB1, play roles in remodeling the tumor microenvironment, highlighting potential implications for immunotherapy strategies.<br /><br />The study employed multiplex immunofluorescence staining to explore the tumor microenvironment, particularly the recruitment of T cells. In the FGF/FGFR/NOTCH1 within RB1 variant group, higher infiltration of CD8 T cells, both exhausted and non-exhausted, was observed, suggesting significant microenvironmental changes that may impact therapeutic approaches.<br /><br />Conclusively, this comprehensive analysis reveals critical insights into the prognostic and microenvironmental aspects of FGF/FGFR signaling alterations in NSCLC, potentially guiding future therapeutic strategies. The research emphasizes the significance of genetic variations and their co-mutations in understanding the disease's progression and treatment, underscoring the necessity for tailored therapeutic interventions.

Asset Subtitle

Ziling Huang

Meta Tag

Speaker Ziling Huang

Topic Pathology & Biomarkers

Keywords

FGF

FGFR

NSCLC

next-generation sequencing

tumor microenvironment

KRAS

prognosis

immunotherapy

T cells

genetic variations