Abstract
Liver fibrosis is characterized by an abnormal accumulation of extracellular matrix proteins, leading to impaired liver function. The pyruvate dehydrogenase alpha 1 (PDHA1) gene, encoding the E1 alpha subunit of the pyruvate dehydrogenase complex, has demonstrated reduced expression in pulmonary fibrosis, suggesting a protective role in fibrotic diseases. This study aimed to identify PDHA1-related gene signatures and explore potential targets for liver fibrosis treatment. Datasets GSE15654 and GSE84044 were sourced from the gene expression omnibus database. Prognostic genes were identified through Pearson correlation analysis, LASSO, and Cox regression in the discovery dataset (GSE15654) and validated using the verification dataset (GSE84044). A prognostic model was constructed and validated with quantitative reverse transcriptase-PCR analysis on surgical resection samples. High PDHA1 expression correlated with improved prognosis in liver fibrosis. Four PDHA1-related prognostic genes (ALDH9A1, ARG1, APOH, and FABP1) were identified as protective factors. Our model accurately predicted patient prognosis, and initial validation with clinical samples supported these conclusions. The prognostic model based on PDHA1-related genes (ALDH9A1, ARG1, APOH, and FABP1) effectively predicts liver fibrosis progression and prognosis. This research provides a novel approach for liver fibrosis prediction and potential treatment strategies.