EXOSC10 是一种新型的肝细胞癌预后生物标志物：全面的生物信息学分析和实验验证。

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor. There are few studies on EXOSC10 (exosome component 10) in HCC; however, the importance of EXOSC10 for HCC remains unclear. METHODS: In the study, the prognosis value of EXOSC10 and the immune correlation were explored by bioinformatics. The expression of EXOSC10 was verified by tissue samples from clinical patients and in vitro experiment (liver cancer cell lines HepG2, MHCC97H and Huh-7; normal human liver cell line LO2). Immunohistochemistry (IHC) was used to detect EXOSC10 protein expression in clinical tissue from HCC. Huh-7 cells with siEXOSC10 were constructed using lipofectamine 3000. Cell counting kit 8 (CCK-8) and colony formation were used to test cell proliferation. The wound healing and transwell were used to analyze the cell migration capacity. Mitochondrial membrane potential, Hoechst 33342 dye, and flow cytometer were used to detect the change in cell apoptosis, respectively. Differential expression genes (DEGs) analysis and gene set enrichment analysis (GSEA) were used to investigate the potential mechanism of EXOSC10 and were verified by western blotting. RESULTS: EXOSC10 was highly expressed in tissues from patients with HCC and was an independent prognostic factor for overall survival (OS) in HCC. Increased expression of EXOSC10 was significantly related to histological grade, T stage, and pathological stage. Multivariate analysis indicated that the high expression level of EXOSC10 was correlated with poor overall survival (OS) in HCC. GO and GSEA analysis showed enrichment of the cell cycle and p53-related signaling pathway. Immune analysis showed that EXOSC10 expression was a significant positive correlation with immune infiltration in HCC. In vitro experiments, cell proliferation and migration were inhibited by the elimination of EXOSC10. Furthermore, the elimination of EXOSC10 induced cell apoptosis, suppressed PARP, N-cadherin and Bcl-2 protein expression levels, while increasing Bax, p21, p53, p-p53, and E-cadherin protein expression levels. CONCLUSIONS: EXOSC10 had a predictive value for the prognosis of HCC and may regulate the progression of HCC through the p53-related signaling pathway.

背景：肝细胞癌（HCC）是一种常见的恶性肿瘤。目前关于 EXOSC10（外泌体成分 10）在 HCC 中的研究较少，但 EXOSC10 对 HCC 的重要性尚不清楚。

方法：本研究通过生物信息学探讨 EXOSC10 的预后价值及其与免疫的相关性。通过临床患者和体外实验（肝癌细胞系 HepG2、MHCC97H 和 Huh-7；正常人类肝细胞系 LO2）的组织样本验证 EXOSC10 的表达。免疫组织化学（IHC）检测 HCC 临床组织中 EXOSC10 蛋白的表达。采用脂质体 3000 构建 siEXOSC10 的 Huh-7 细胞。细胞计数试剂盒 8（CCK-8）和集落形成实验用于检测细胞增殖。划痕愈合和 Transwell 用于分析细胞迁移能力。线粒体膜电位、Hoechst 33342 染料和流式细胞术分别用于检测细胞凋亡的变化。差异表达基因（DEGs）分析和基因集富集分析（GSEA）用于研究 EXOSC10 的潜在机制，并通过 Western blot 进行验证。

结果：EXOSC10 在 HCC 患者的组织中高表达，是 HCC 总生存期（OS）的独立预后因素。EXOSC10 的高表达与组织学分级、T 分期和病理分期显著相关。多因素分析表明，EXOSC10 的高表达水平与 HCC 患者的总生存（OS）不良相关。GO 和 GSEA 分析表明细胞周期和 p53 相关信号通路富集。免疫分析表明，EXOSC10 表达与 HCC 中的免疫浸润呈显著正相关。体外实验中，消除 EXOSC10 可抑制细胞增殖和迁移。此外，消除 EXOSC10 诱导细胞凋亡，抑制 PARP、N-钙粘蛋白和 Bcl-2 蛋白表达水平，同时增加 Bax、p21、p53、p-p53 和 E-钙粘蛋白蛋白表达水平。

结论：EXOSC10 对 HCC 的预后有预测价值，可能通过 p53 相关信号通路调节 HCC 的进展。