肝纤维化对肝细胞癌（HCC）恶化的影响仍存在争议。我们希望通过建立纤维化-缺氧-糖酵解-免疫相关的预后模型来探讨这个问题。使用分子特征数据库中的肝纤维化相关基因来评估 TCGA 数据库中 HCC 患者的纤维化程度。使用基于算法均匀流形近似和投影（UMAP）的纤维化相关表达矩阵将患者分为两组，并通过 UMAP 聚类和基因富集分析评估纤维化情况。通过差异分析、LASSO和多元回归分析构建预后模型。通过 CIBERSORT 进行免疫浸润分析。采用定量PCR和免疫组化方法检测我院HCC患者的基因表达水平。在TCGA数据库的365名HCC患者中，基于129个与肝纤维化相关的基因，111名高纤维化评分的HCC患者的预后比低纤维化患者的预后更差，这可能是由纤维化、血管生成、缺氧、糖酵解、炎症反应和高免疫浸润。我们构建了纤维化-缺氧-糖酵解-免疫预后模型（FHGISig），该模型可以显着预测 HCC 患者的疾病进展。此外，我们揭示了 FHGISig 与免疫细胞浸润水平以及免疫检查点之间的密切相关性。最后，PCR结果发现，与非肝硬化患者相比，肝硬化HCC患者的TFF3 mRNA显着降低。肝纤维化是 HCC 的不良预后因素，我们的 FHGISig 可以显着预测疾病进展，这也可能成为 HCC 患者免疫治疗的潜在预测标记。版权所有 © 2023 Elsevier B.V. 保留所有权利。

The impact of liver fibrosis on the deterioration of hepatocellular carcinoma (HCC) remains controversial. We hope to explore this issue through establishing a fibrosis-hypoxia-glycolysis-immune related prognostic model. Liver fibrosis-related genes from Molecular Signatures Database were used to evaluate the degree of fibrosis in HCC patients from the TCGA database. The patients were divided into two groups using the fibrosis-related expression matrix based on the algorithm uniform manifold approximation and projection (UMAP) and evaluated for fibrosis by UMAP cluster and gene enrichment analysis. Prognostic model was constructed by differential analysis, LASSO, and multivariate regression analysis. Immune-infiltration analysis was performed by CIBERSORT. Quantitative PCR and immunohistochemistry were performed to measure the gene expression levels in HCC patients from our hospital. In 365 HCC patients from the TCGA database, 111 HCC patients with high fibrosis score have a worse prognosis than those with low fibrosis based on 129 genes related to liver fibrosis, which may be caused by the interaction between fibrosis, angiogenesis, hypoxia, glycolysis, inflammatory response, and high immune infiltration. We constructed a Fibrosis-Hypoxia-Glycolysis-Immune Prognostic Model (FHGISig), which could significantly predict disease progression in HCC patients. Furthermore, we revealed a close correlation between FHGISig and immune cell infiltration level as well as immune checkpoints. Finally, PCR results found TFF3 mRNA was significantly lower in cirrhotic HCC patients compared with non-cirrhotic ones. Liver fibrosis is a poor-prognostic factor for HCC, and our FHGISig could significantly predict disease progression, which could also be a potential predictive marker for immunotherapy in HCC patients.Copyright © 2023 Elsevier B.V. All rights reserved.