Abstract 4506: Plasma proteomics reveals biomarkers of lung cancer in non-smoking women

Abstract Background: Lung cancer is the most prevalent cancer among women in China. The incidence of lung cancer in women is increasing, despite the fact that traditional risk factors such as smoking have decreased. The investigation of new protein markers may enhance the etiological network and further elucidate the pathogenesis of lung cancer in non-smoking women. Methods: We selected three non-smoking female lung cancer patients from the Chinese Colorectal, Breast, Lung, Liver, And Stomach Cancer Screening Trial (C-BLAST) cohort. Three healthy controls were matched based on age (±3 years), sex, year of screening, and smoking status. The proteomic assays were conducted on the Somascan Assay 11k platform, utilizing plasma that had been collected at baseline. The differential proteins between lung cancer patients and healthy controls were analyzed using paired t-tests (P < 0.05). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) platforms were employed to investigate the functions and pathways enriched by differential proteins. The STRING platform was utilized to develop the protein-protein interaction (PPI) network of these proteins, and the core proteins were determined based on their degree. Results: The average age of the participants in the study was 55.8 years. Through the comparison of plasma proteomics between lung cancer patients and healthy controls, 224 differential proteins were discovered, including 116 up-regulated and 108 down-regulated proteins. GO analysis revealed these proteins were associated with some biological functions, including the response to hydrogen peroxide, nuclear-transcribed mRNA catabolic process, exonucleolytic, fatty acid homeostasis, immune effector processes, and T-helper 2 cell differentiation. KEGG analysis revealed that these proteins are enriched in pathways such as glycerolipid metabolism, aldosterone-regulated sodium reabsorption, transcriptional dysregulation in cancer, and NOD-like receptor signaling pathway. We constructed the PPI network based on these 224 proteins and identified the top ten core proteins: CD4, INS, MYD88, IFNA1, APOE, BECN1, CD86, MPHOSPH10, NLRP3, and C3. These core proteins are involved in biological processes, including immunology, inflammation, and antiviral responses, and may contribute to the development of lung cancer. Conclusions: We found several plasma proteins by plasma proteomics that may assist in identifying lung cancer patients and offer new insights into the etiological network of non-smoking lung cancer in women. Citation Format: Guojin Si, Zhangyan Lyu, Ximin Gao, Fengju Song. Plasma proteomics reveals biomarkers of lung cancer in non-smoking women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4506.