Gao Xueke, Xu Yangtao, Hu Xinyao, Chen Jiayu, Zhang Daoming, Xu Ximing
Renmin Hospital of Wuhan University, Wuhan, Hubei, China 430060.
Renmin Hospital of Wuhan University, Wuhan, Hubei, China 430060.
Gene. 2025 Apr 10;944:149299. doi: 10.1016/j.gene.2025.149299. Epub 2025 Jan 30.
The mitochondrial solute carrier family 25 (SLC25) is known to play a pivotal role in oncogenesis, yet its specific involvement in hepatocellular carcinoma (HCC) remains poorly elucidated.
In this study, we performed a clustering analysis of HCC patients in the Cancer Genome Atlas database based on the expression levels of SLC25 members, and conducted clinical feature analysis for each patient within the clusters. Subsequently, we developed a prognostic model using a Lasso regression approach with SLC25A19, SLC25A49, and SLC25A51 as features, and generated a risk score for each HCC patient. We then identified SLC25A19 as a potential prognostic marker for HCC through single-cell analysis, and validated this finding using in vitro and in vivo experiments.
Our results revealed significant differences in the expression of most SLC25 family members in HCC patients, enabling the stratification of patients into three clusters, with those in cluster 1 exhibiting the most favorable prognosis and showing a correlation with enhanced immune infiltration. The risk scores derived from the features SLC25A19, SLC25A49, and SLC25A51 effectively predicted the prognosis of HCC patients, with area under the curve (AUC) values exceeding 0.7 in the test group. Single-cell analysis further demonstrated h eightened expression of SLC25A19 in the immune microenvironment of HCC, and in vitro experiments indicated that SLC25A19 may regulate the proliferation, migration, invasion, cycle, and apoptosis of liver cancer cells through the Wnt pathway. In the HepG2 animal model, overexpression of SLC25A19 significantly promotes tumor growth, while knockdown inhibits tumor growth. Analysis of patient tumor tissues shows that SLC25A19 is highly expressed in liver cancer tissues and is associated with CD8 T cell infiltration.
In conclusion, our comprehensive analysis of the role of SLC25 in HCC unveiled SLC25A19 as a potential regulatory factor in HCC.
线粒体溶质载体家族25（SLC25）在肿瘤发生中起关键作用，但其在肝细胞癌（HCC）中的具体作用仍不清楚。
在本研究中，我们基于SLC25成员的表达水平对癌症基因组图谱数据库中的肝癌患者进行聚类分析，并对聚类中的每位患者进行临床特征分析。随后，我们以SLC25A19、SLC25A49和SLC25A51为特征，采用套索回归方法建立了一个预后模型，并为每位肝癌患者生成了一个风险评分。然后，我们通过单细胞分析将SLC25A19鉴定为肝癌的潜在预后标志物，并通过体外和体内实验验证了这一发现。
我们的结果显示，大多数SLC25家族成员在肝癌患者中的表达存在显著差异，患者可分为三个聚类，其中聚类1的患者预后最佳，且与免疫浸润增强相关。由SLC25A19、SLC25A49和SLC25A51特征得出的风险评分有效地预测了肝癌患者的预后，测试组的曲线下面积（AUC）值超过0.7。单细胞分析进一步表明，SLC25A19在肝癌的免疫微环境中表达升高，体外实验表明，SLC25A19可能通过Wnt途径调节肝癌细胞的增殖、迁移、侵袭、周期和凋亡。在HepG2动物模型中，SLC25A19的过表达显著促进肿瘤生长，而敲低则抑制肿瘤生长。对患者肿瘤组织的分析表明，SLC25A19在肝癌组织中高表达，且与CD8 T细胞浸润相关。
总之，我们对SLC25在肝癌中的作用进行的综合分析揭示了SLC25A19是肝癌的潜在调节因子。
