West China School of Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Mol Med Rep. 2024 May;29(5). doi: 10.3892/mmr.2024.13203. Epub 2024 Mar 22.
Hepatocellular carcinoma (HCC) is a common malignancy with a poor prognosis, and its heterogeneity affects the response to clinical treatments. Glycolysis is highly associated with HCC therapy and prognosis. The present study aimed to identify a novel biomarker for HCC by exploring the heterogeneity of glycolysis in HCC. The intersection of both marker genes of glycolysis‑related cell clusters from single‑cell RNA sequencing analysis and mRNA data of liver HCC from The Cancer Genome Atlas were used to construct a prognostic model through Cox proportional hazard regression and the least absolute shrinkage and selection operator Cox regression. Data from the International Cancer Genome Consortium were used to validate the results of the analysis. Immune status analysis was then conducted. A significant gene in the prognostic model was identified as a potential biomarker and was verified through experiments. The results revealed that the glycolysis‑related prognostic model divided patients with HCC into high‑ and low‑risk groups. A nomogram combining the model and clinical features exhibited accurate predictive ability, with an area under the curve of 0.763 at 3 years. The high‑risk group exhibited a higher expression of checkpoint genes and lower tumor immune dysfunction and exclusion scores, suggesting that this group may be more likely to benefit from immunotherapy. The tumor tissues had a higher zinc finger protein (ZFP)41 mRNA and protein expression compared with the adjacent tissues. analyses revealed that ZFP41 played a crucial role in cell viability, proliferation, migration, invasion and glycolysis. On the whole, the present study demonstrates that the glycolysis‑related prognostic gene, ZFP41, is a potential prognostic biomarker and therapeutic target, and may play a crucial role in glycolysis and malignancy in HCC.
肝细胞癌 (HCC) 是一种预后不良的常见恶性肿瘤，其异质性影响临床治疗的反应。糖酵解与 HCC 治疗和预后高度相关。本研究旨在通过探索 HCC 中糖酵解的异质性，确定 HCC 的新型生物标志物。通过 Cox 比例风险回归和最小绝对收缩和选择算子 Cox 回归，使用单细胞 RNA 测序分析中糖酵解相关细胞簇的标记基因和癌症基因组图谱中肝脏 HCC 的 mRNA 数据的交集构建预后模型。使用国际癌症基因组联盟的数据验证分析结果。然后进行免疫状态分析。在预后模型中确定一个重要基因作为潜在的生物标志物，并通过实验进行验证。结果表明，糖酵解相关的预后模型将 HCC 患者分为高风险和低风险组。结合模型和临床特征的列线图显示出准确的预测能力，3 年时的曲线下面积为 0.763。高风险组的检查点基因表达更高，肿瘤免疫功能障碍和排除评分更低，这表明该组可能更受益于免疫治疗。肿瘤组织的锌指蛋白 (ZFP)41 mRNA 和蛋白表达高于相邻组织。分析表明，ZFP41 在细胞活力、增殖、迁移、侵袭和糖酵解中发挥着关键作用。总的来说，本研究表明，与糖酵解相关的预后基因 ZFP41 是一个潜在的预后生物标志物和治疗靶点，可能在 HCC 中的糖酵解和恶性肿瘤中发挥关键作用。
