Weber Florian, Evert Katja, Scheiter Alexander, von Sachsen-Coburg Sophie, Utpatel Kirsten, Buechler Christa
Institute of Pathology, University of Regensburg, 93053 Regensburg, Germany.
Department of Internal Medicine I, Regensburg University Hospital, 93053 Regensburg, Germany.
Biomedicines. 2025 Jul 13;13(7):1707. doi: 10.3390/biomedicines13071707.
The Niemann-Pick C1 (NPC1) protein regulates cellular cholesterol homeostasis, which is disrupted in hepatocellular carcinoma (HCC). Sex differences in cholesterol metabolism may also be related to NPC1 expression in HCC. A sex-specific analysis was, therefore, performed to investigate this further. The expression of NPC1 protein in hepatocytes was assessed using immunohistochemistry in HCC tissues from 264 male and 59 female patients, as well as in non-tumor tissues from 41 males and 7 females. The disease etiology was documented for 40% of these patients, and NPC1 protein levels in the tumors of patients with alcoholic, metabolic, and viral liver disease were comparable. The severity of underlying liver fibrosis was similar in both females and males. No difference in hepatocyte NPC1 protein expression was observed between males and females in non-tumor and tumor tissues. However, NPC1 expression was strongly increased in tumor tissues in both sexes. NPC1 protein levels were positively associated with T stage and Union for International Cancer Control (UICC) stage in both sexes. NPC1 protein levels were negatively correlated with overall survival, recurrence-free survival, and metastasis-free survival time in males only. Univariate Cox regression analysis showed a significant association of NPC1 protein levels with metastasis-free survival in males. Positive correlations of NPC1 protein with tumor size and negative associations with tumor inflammation were observed only in women. This study showed that hepatocyte NPC1 protein levels are highly elevated in HCC tissue in both sexes but are more closely associated with survival in male patients than in female patients.
尼曼-匹克C1（NPC1）蛋白调节细胞胆固醇稳态，而肝细胞癌（HCC）中该稳态被破坏。胆固醇代谢的性别差异也可能与HCC中NPC1的表达有关。因此，进行了一项性别特异性分析以进一步研究这一问题。使用免疫组织化学方法评估了264例男性和59例女性患者的HCC组织以及41例男性和7例女性的非肿瘤组织中肝细胞内NPC1蛋白的表达。记录了40%这些患者的疾病病因，酒精性、代谢性和病毒性肝病患者肿瘤中的NPC1蛋白水平相当。男性和女性潜在肝纤维化的严重程度相似。在非肿瘤组织和肿瘤组织中，未观察到男性和女性肝细胞NPC1蛋白表达存在差异。然而，两性肿瘤组织中NPC1表达均显著增加。NPC1蛋白水平在两性中均与T分期和国际癌症控制联盟（UICC）分期呈正相关。仅在男性中，NPC1蛋白水平与总生存期、无复发生存期和无转移生存期呈负相关。单因素Cox回归分析显示NPC1蛋白水平与男性无转移生存期显著相关。仅在女性中观察到NPC1蛋白与肿瘤大小呈正相关，与肿瘤炎症呈负相关。这项研究表明，两性HCC组织中肝细胞NPC1蛋白水平均高度升高，但与男性患者生存期的相关性比女性患者更为密切。
