TFCP2 is recognized as a dynamic monitoring index of pneumoconiosis by combining radiomics with transcriptomics.

Objective: Herein, we employed a novel integrated radiomics and transcriptomics approach to identify key biomarkers for pneumoconiosis. Specifically, we combined thoracic Computed Tomography (CT) imaging-based phenomics and peripheral blood gene expression analysis to improve early diagnosis and risk stratification of pneumoconiosis.

Methods: The study cohort comprised individuals with diagnosed pneumoconiosis and healthy coal miners. Participants were categorized into low-, medium-, and high-risk groups, as well as a pneumoconiosis group, based on radiomics scoring. Peripheral blood samples were collected for transcriptome sequencing analysis, and key genes were selected through differential expression and trend analysis. Mfuzz clustering analysis and KEGG pathway enrichment analysis were utilized to further investigate gene expression patterns and functions. The expression of key genes was verified using real-time quantitative PCR and western blotting. The diagnostic value of key genes was assessed using Receiver Operating Characteristic (ROC) analysis. A mouse model was constructed to assess the role of TFCP2 in pneumoconiosis and to explore its potential mechanisms.

Results: Our findings revealed that heterogeneous gene expression patterns correlated with an increased pneumoconiosis risk. Additionally, TFCP2 emerged as a significant biomarker (AUC = 0.799), with its expression levels increasing with pneumoconiosis risk. Furthermore, TFCP2 upregulation correlated closely with Extracellular Matrix (ECM)-receptor interactions and AGE-RAGE signaling pathways, which have been associated with fibrosis and inflammatory responses in lung tissue. Moreover, silencing TFCP2 in a mouse model improved silica-induced pulmonary fibrosis, with USP22 identified as a downstream target gene of TFCP2.

Conclusion: TFCP2 may serve as a potential biomarker and therapeutic target for the progression of pneumoconiosis. Its high expression in lung epithelial cells may exacerbate pulmonary fibrosis by promoting EMT and ECM deposition. This study provides new molecular targets for the early diagnosis and treatment of pneumoconiosis.