iProXProteomicsChao CaoHomo Sapienshttp://www.iprox.org/page/project.html?id=IPX0014400000caocdoctor@163.comThe First Affiliated Hospital of Ningbo UniversityiProXDistinguishing indeterminate pulmonary nodules remains a significant challenge in the early diagnosis of lung cancer. This study aims to identify lobe-specific proteomic biomarkers to address this issue. Using a data-independent acquisition (DIA) strategy, we performed proteomic profiling of bronchoalveolar lavage fluid (BALF) obtained from the lesioned lobe of lung cancer patients (LC-L), their paired nonlesioned lobe (LC-N), and the lesioned lobe of patients with benign nodules (BN-L). We quantified 4,305 proteins and identified 134 upregulated and 44 downregulated proteins in LC-L compared to both control groups (<i>p</i> < 0.05; |FC| > 1.2). Pathway analysis revealed significant enrichment of these dysregulated proteins in metabolic pathways and the TCA cycle. Subsequent validation in an independent cohort confirmed that two candidate proteins, SUCLA2 and FKBP9, were significantly upregulated specifically in cancerous lobes. To our knowledge, this is the first report identifying SUCLA2 and FKBP9 as lung cancer-specific biomarkers detectable in BALF using a self-controlled study design. These findings provide crucial insights into the metabolic reprogramming of early stage lung cancer and offer promising novel targets for improving the differential diagnosis of indeterminate pulmonary nodules.Discovery and Validation of Lung Cancer Biomarkers Based on Proteomic Analysis of Bronchoalveolar Lavage Fluid from the Self-Controlled Pulmonary Lobes.Wei Shihui S, Chen Tianwei T, Jin Yan Y, Jin Xiaoyan X, Zhao Yun Y, Chen Xingyu X, Cao Qianhua Q, Li Liucheng L, Zhou Mengli M, Qi Rongbin R, Cao Chao CfalseDiscovery and validation of lung cancer biomarkers based on proteomic analysis of bronchoalveolar lavage fluid from the self-controlled pulmonary lobeBackground: Distinguishing indeterminate pulmonary nodules remains a significant challenge in the early diagnosis of lung cancer, while proteomic biomarkers derived from the lesioned pulmonary lobe may provide crucial insights into their malignant progression. Methods: Our study cohort included three groups: the lesioned lobe of lung cancer patients (LC-L), the paired non-lesioned lobe of lung cancer patients (LC-N), and the lesioned lobe of patients with benign nodules (BN-L). Data-independent acquisition (DIA) proteomic analysis was performed to identify potential biomarkers for early diagnosis of lung cancer, followed by evaluation in a larger, independent cohort. Results: We identified 4,305 proteins, among which 715 and 738 were differentially expressed between LC-L and LC-N, and between LC-L and BN-L, respectively. Integration of these results revealed 134 up-regulated and 44 down-regulated proteins (p < 0.05; |FC| > 1.2). Notably, 14 proteins exhibited a |FC| > 3, and 5 of them were either involved in biological metabolism or had been previously reported as cancer-associated. KEGG pathway enrichment analysis of the 134 up-regulated proteins demonstrated significant enrichment in metabolic pathways and the TCA cycle. We further validated 9 candidate proteins by ELISA and confirmed that 3 proteins (SUCLA2, FKBP9, TAP1) exhibited expression patterns consistent with those observed in the discovery cohort. Among them, SUCLA2 and FKBP9 reached statistical significance, while TAP1 showed a strong trend (p = 0.061). To our knowledge, this is the first report showing that SUCLA2 and FKBP9 are up-regulated in the lesioned lobes of lung cancer patients, independent of benign nodules. Conclusions: These candidate biomarkers and their associated metabolic reprogramming pathways provide a new direction for improving the identification ability of uncertain nodules, and expand our understanding of the pathophysiology of early lung cancer.Tue Nov 25 00:00:00 GMT 2025PXD071235960641921188