Abstract 1887: Proteomics unveil characteristic proteins of patients with benign and malignant pulmonary nodules

Abstract Background: LDCT screening can significantly lower the mortality rate of lung cancer among high-risk individuals. Nevertheless, the limitations of CT might lead to frequent follow-up examinations and false positive outcomes, thereby causing unnecessary interventions and overtreatment. Therefore, the development of reliable and convenient biomarkers to accurately differentiate between benign and malignant nodules and to assess the likelihood of cancerous transformation is essential. We attempted to provide meaningful biomarkers based on plasma proteomic studies. Methods: The participants in this study were chosen from individuals aged 40 to 74 years in the Chinese Colorectal, Breast, Lung, Liver, And Stomach Cancer Screening Trial (C-BLAST). We selected 10 patients with malignant lung nodules and 10 with benign lung nodules, matched for age and sex. Malignant lung nodules were defined as those with a LUNG-RADS diagnostic category of 4A, 4B, or 4X, accompanied by a biopsy confirming malignancy; benign nodules were those with a diagnostic category not exceeding 3. Plasma samples from two groups were collected and subjected to proteomic analysis using the Somascan Assay 11k detection platform. Paired t-tests were employed to identify the differential proteins between malignant and benign pulmonary nodules. The functional pathways enriched by these proteins were determined based on Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Finally, the STRING was utilized to construct a protein-protein interaction network (PPI) and determine the key proteins related to malignant nodules. Results: The average age of both groups was 61.4 years. A comparison of the proteomics between the malignant pulmonary nodule group and the benign pulmonary nodule group identified 188 differentially expressed proteins (P < 0.05), among which 102 were up-regulated proteins and 86 were down-regulated proteins. GO analysis of the differential proteins indicated functional enrichment in pathways such as chemical carcinogenesis, fluid shear stress and atherosclerosis, and biosynthesis of cofactors. According to KEGG analysis, they were mainly enriched in pathways like chemical carcinogenesis-reactive oxygen species, fluid shear stress and atherosclerosis, and metabolism of xenobiotics by cytochrome P450. Through PPI analysis, ten key proteins were determined, including CRP, FCGR3B, CCL2, CYP3A5, GSTA3, GSTM1, GSTM3, GSTM5, CD163, and GSTM4. These molecules possess anti-atherosclerotic and anti-inflammatory activities, as well as chemotactic activity for monocytes and basophils, and play roles in hydrolyzing nucleotides and host defense. Conclusions: Our research results provide ten potential plasma protein biomarkers for the discrimination of benign and malignant pulmonary nodules, which might broaden our understanding of their characteristics. Citation Format: Ximin Gao, Zhangyan Lyu, Guojin Si, Fengju Song. Proteomics unveil characteristic proteins of patients with benign and malignant pulmonary nodules [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 1887.