肝癌是一种狡猾的恶性疾病，在全球范围内的癌症中发病率和死亡率均较高。NPC基因家族成员（NPCs：NPC1、NPC2和NPC1L1）与多种癌症的发展密切相关，但它们在肝癌中的作用尚不清楚。因此，我们必须研究它们在肝细胞肝癌（LIHC）中的功能。NPCs在正常组织和LIHC组织之间的差异表达显著，在LIHC中突变频率较高。ROC曲线分析表明，NPC1/NPC2在LIHC中具有较高的诊断和预后价值。NPC1的表达与其甲基化水平呈负相关。在LIHC的高、低NPC1表达组之间的差异表达基因主要与通道活性、转运复合物和细胞膜粘附分子相关。此外，NPC1表达与多种免疫细胞和免疫检查点显著关联。据推测，TUG1/SNHG4-miR-148a-3p-NPC1调控轴与肝癌发生密切相关。最后，检测了LIHC组织和癌旁组织中NPC1的蛋白表达，并发现NPC1敲除（NPC1KO）的HepG2细胞抑制了细胞的增殖、迁移和侵袭。本研究有助于鉴定LIHC的新的预后标志物和潜在的免疫治疗靶点，揭示了NPC1在LIHC中的分子调控机制。NPCs在LIHC的预后和诊断中起着关键作用，并可能成为LIHC预后和诊断的重要指标；NPC1可能是LIHC的潜在治疗靶点。© 2023. 作者，Springer-Verlag GmbH Germany的独家许可，属于Springer Nature的一部分。

Liver cancer is a cunning malignancy with a high incidence and mortality rate among cancers worldwide. The NPC gene family members (NPCs: NPC1, NPC2, and NPC1L1) are closely linked to the development of multiple cancers, but their role in liver cancer remains unclear. As a result, we must investigate their functions in liver hepatocellular carcinoma (LIHC). NPCs were significantly differentially expressed between normal and LIHC tissues, with a high mutation frequency in LIHC. The ROC curve analysis revealed that NPC1/NPC2 had high diagnostic and prognostic values in LIHC. NPC1 expression was also found to be negatively correlated with its methylation level. The differentially expressed genes between high and low NPC1 expression groups in LIHC were mainly related to channel activity, transporter complexes, and plasma membrane adhesion molecules. Additionally, NPC1 expression was significantly associated with multiple immune cells and immunization checkpoints. It was hypothesized that a TUG1/SNHG4-miR-148a-3p-NPC1 regulatory axis is associated with hepatocarcinogenesis. Finally, the protein expression of NPC1 in LIHC tissues and paraneoplastic tissues was detected, and NPC1-knockdown HepG2 cells (NPC1KO) inhibited the proliferation, migration, and invasion. This study helped to identify new prognostic markers and potential immunotherapeutic targets for LIHC and revealed the molecular mechanisms underlying NPC1 regulation in LIHC. The NPCs play a key role in the prognosis and diagnosis of LIHC and may be an important indicator for LIHC prognosis and diagnosis; NPC1 might be a potential therapeutic target in LIHC.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.