简介：肝细胞癌（HCC）是最常见的肝癌，与慢性炎症密切相关，主要涉及癌前微环境中免疫反应失调。目前，大多数研究仅限于 HCC 发病率。然而，癌前病变的免疫致病机制仍不清楚。方法：我们从两个非酒精性脂肪性肝病（NAFLD）肝硬化样本和五个健康样本中获得了单细胞测序数据（GSE136103）。使用伪时间分析，我们系统地识别了五种不同的 T 细胞分化状态。在 81 种组合中使用了 10 种机器学习算法来整合框架，并在多队列批量转录组分析中建立最佳的 T 细胞分化相关预后特征。结果：LDHA 被认为是核心基因，并且使用多个外部数据集验证了结果。此外，我们使用免疫组织化学和流式细胞术验证了 LDHA 表达。结论：LDHA 是 T 细胞中 NAFLD 肝硬化进展为 HCC 的关键标记基因。版权所有 © 2024 Wang、Ye、Ning、Zhang、Lv、Li 和 Wang。

Introduction: Hepatocellular carcinoma (HCC), which is closely associated with chronicinflammation, is the most common liver cancer and primarily involves dysregulated immune responses in the precancerous microenvironment. Currently, most studies have been limited to HCC incidence. However, the immunopathogenic mechanisms underlying precancerous lesions remain unknown. Methods: We obtained single-cell sequencing data (GSE136103) from two nonalcoholic fatty liver disease (NAFLD) cirrhosis samples and five healthy samples. Using pseudo-time analysis, we systematically identified five different T-cell differentiation states. Ten machine-learning algorithms were used in 81 combinations to integrate the frameworks and establish the best T-cell differentiation-related prognostic signature in a multi-cohort bulk transcriptome analysis. Results: LDHA was considered a core gene, and the results were validated using multiple external datasets. In addition, we validated LDHA expression using immunohistochemistry and flow cytometry. Conclusion: LDHA is a crucial marker gene in T cells for the progression of NAFLD cirrhosis to HCC.Copyright © 2024 Wang, Ye, Ning, Zhang, Lv, Li and Wang.