WCLC 2025 - Posters & ePosters-P3.03.09 Synonymous Mutations in PDGFRA Exons 12 and 18 Correlate With Reduced Survival and Serum Iron Levels in Non-Small Cell Lung Cancer

P3.03.09 Synonymous Mutations in PDGFRA Exons 12 and 18 Correlate With Reduced Survival and Serum Iron Levels in Non-Small Cell Lung Cancer

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This study investigates the impact of synonymous mutations in PDGFRA exons 12 and 18 on survival outcomes and serum iron levels in advanced non-small cell lung cancer (NSCLC). Using second-generation gene sequencing on 302 untreated advanced NSCLC patients, the researchers examined gene mutation profiles, smoking status, serum iron levels, and treatment responses.<br /><br />Key findings reveal that the presence of synonymous mutations in PDGFRA exons 12 and 18 correlates with poorer overall survival, with exon 18 mutations further aggravating outcomes in patients already harboring exon 12 mutations. These PDGFRA mutations are more commonly found in smokers and are associated with primary resistance to first-line chemoimmunotherapy. Notably, patients with both exon 12 and 18 mutations exhibited significantly decreased baseline serum iron levels, and low serum iron independently predicted worse prognosis.<br /><br />PDGFRA encodes a receptor critical for platelet-derived growth factor signaling, which influences tumor angiogenesis, microenvironment maintenance, and vascular development. While synonymous mutations do not alter protein sequences, emerging evidence indicates they can affect gene expression and protein function, contributing to disease progression and treatment resistance.<br /><br />Statistical analyses, including logistic regression, chi-square, and survival tests, supported these findings, suggesting that these co-occurring synonymous mutations could impair treatment efficacy through mechanisms possibly involving serum iron depletion. The study underscores the need for further molecular investigation into how PDGFRA synonymous mutations affect tumor biology and iron metabolism in NSCLC.<br /><br />In conclusion, coexisting synonymous mutations in PDGFRA exons 12 and 18 serve as biomarkers for reduced survival and treatment resistance in advanced NSCLC, potentially mediated by serum iron depletion. These findings offer new insights into genetic factors influencing prognosis and highlight the importance of exploring targeted therapeutic strategies addressing these molecular alterations.

Asset Subtitle

Xiaowei He

Meta Tag

Speaker Xiaowei He

Topic Tumor Biology – Translational Biology

Keywords

PDGFRA synonymous mutations

exon 12 mutations

exon 18 mutations

non-small cell lung cancer

NSCLC prognosis

serum iron levels

treatment resistance

chemoimmunotherapy

smoking status

gene sequencing