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肝纤维化中与PDHA1相关的预后基因的探索

Exploration of PDHA1-related prognostic genes in liver fibrosis.

作者信息

Zhao Yu, Li Keyu

机构信息

Department of General Surgery, West China Tianfu Hospital, Sichuan University, Chengdu, China.

Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China.

出版信息

Medicine (Baltimore). 2025 Jun 6;104(23):e42769. doi: 10.1097/MD.0000000000042769.

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.

摘要

肝纤维化的特征是细胞外基质蛋白异常积累,导致肝功能受损。编码丙酮酸脱氢酶复合体E1α亚基的丙酮酸脱氢酶α1(PDHA1)基因在肺纤维化中表达降低,提示其在纤维化疾病中具有保护作用。本研究旨在识别与PDHA1相关的基因特征,并探索肝纤维化治疗的潜在靶点。数据集GSE15654和GSE84044来自基因表达综合数据库。在发现数据集(GSE15654)中通过Pearson相关分析、LASSO和Cox回归识别预后基因,并在验证数据集(GSE84044)中进行验证。构建了一个预后模型,并通过对手术切除样本的定量逆转录聚合酶链反应分析进行验证。PDHA1高表达与肝纤维化患者预后改善相关。鉴定出四个与PDHA1相关的预后基因(ALDH9A1、ARG1、APOH和FABP1)作为保护因素。我们的模型准确预测了患者预后,临床样本的初步验证支持了这些结论。基于与PDHA1相关基因(ALDH9A1、ARG1、APOH和FABP1)的预后模型有效地预测了肝纤维化的进展和预后。本研究为肝纤维化的预测和潜在治疗策略提供了一种新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf09/12150988/0f00cf42fa08/medi-104-e42769-g001.jpg

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