Eleven metabolism‑related genes composed of Stard5 predict prognosis and contribute to EMT phenotype in HCC.
Eleven metabolism‑related genes composed of Stard5 predict prognosis and contribute to EMT phenotype in HCC.
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DOI：
10.1186/s12935-023-03097-0
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发表时间：
2023-11-17
影响因子：
5.8
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中科院分区：
文献类型：
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肝细胞癌（HCC）是世界范围内最常见的癌症之一，死亡率高，生存率低。异常的肿瘤代谢被认为是HCC的一个标志，也是一个潜在的治疗靶点。本研究旨在鉴定代谢相关的生物标志物，以评估HCC患者的预后。癌症基因组图谱（TCGA）数据库用于探索基于高上皮-间质转化（EMT）分组和低上皮-间质转化（EMT）分组的差异代谢途径。获得不同代谢途径的基因，进行HCC代谢相关分子亚型分析。对三种亚型的差异表达基因（DEGs）进行Lasso Cox回归分析，构建预后风险模型。采用western blot和免疫组化（IHC）检测肝癌患者中Stard5的表达，并通过细胞学实验探讨Stard5在肝癌转移中的作用。基于代谢相关基因的无监督聚类分析显示HCC有三种不同的预后亚型。基于3种deg亚型的LASSO Cox回归分析获得的11个基因（STARD5、FTCD、SCN4A、ADH4、CFHR3、CYP2C9、CCL14、GADD45G、SOX11、SCIN、SLC2A1）构建风险预后模型。我们验证了该模型具有良好的预测能力。此外，我们发现高危组预后较差，Tregs比例较高，对化疗反应较差。我们还发现，Stard5在HCC组织中的表达明显降低，与预后不良和EMT相关。下调Stard5有助于HCC细胞的侵袭和迁移。过表达Stard5可抑制HCC细胞的EMT。我们建立了一个基于11个代谢相关基因的新模型，预测HCC的预后和对化疗或免疫治疗的反应。值得注意的是，我们首次证明了Stard5通过抑制HCC转移而发挥肿瘤抑制作用。在线版本包含补充材料，可在10.1186/s12935-023-03097-0获得。
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, with a high mortality and poor survival rate. Abnormal tumor metabolism is considered a hallmark of HCC and is a potential therapeutic target. This study aimed to identify metabolism-related biomarkers to evaluate the prognosis of patients with HCC. The Cancer Genome Atlas (TCGA) database was used to explore differential metabolic pathways based on high and low epithelial-mesenchymal transition (EMT) groupings. Genes in differential metabolic pathways were obtained for HCC metabolism-related molecular subtype analysis. Differentially expressed genes (DEGs) from the three subtypes were subjected to Lasso Cox regression analysis to construct prognostic risk models. Stard5 expression in HCC patients was detected by western blot and immunohistochemistry (IHC), and the role of Stard5 in the metastasis of HCC was investigated by cytological experiments. Unsupervised clustering analysis based on metabolism-related genes revealed three subtypes in HCC with differential prognosis. A risk prognostic model was constructed based on 11 genes (STARD5, FTCD, SCN4A, ADH4, CFHR3, CYP2C9, CCL14, GADD45G, SOX11, SCIN, and SLC2A1) obtained by LASSO Cox regression analysis of the three subtypes of DEGs. We validated that the model had a good predictive power. In addition, we found that the high-risk group had a poor prognosis, higher proportion of Tregs, and responded poorly to chemotherapy. We also found that Stard5 expression was markedly decreased in HCC tissues, which was associated with poor prognosis and EMT. Knockdown of Stard5 contributed to the invasion and migration of HCC cells. Overexpression of Stard5 inhibited EMT in HCC cells. We developed a new model based on 11 metabolism-related genes, which predicted the prognosis and response to chemotherapy or immunotherapy for HCC. Notably, we demonstrated for the first time that Stard5 acted as a tumor suppressor by inhibiting metastasis in HCC. The online version contains supplementary material available at 10.1186/s12935-023-03097-0.
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