F-box和富含亮氨酸重复序列蛋白5（FBXL5）是一种铁感应的泛素连接酶，可能与肝细胞癌（HCC）的致癌过程有关，因为它扰乱了细胞铁平衡。然而，需要使用患者样本来阐明FBXL5表达的临床意义。我们收集了两所研究机构的HCC组织样本：三星医疗中心（n=259）和哈林大学圣心医院（n=115），并使用免疫组化评估了FBXL5的表达。使用X-tile软件确定的分界值，研究FBXL5表达与几个临床病理参数之间的关联。为了进行外部验证，使用了癌症基因组图谱（TCGA）队列。FBXL5免疫组化表达与无复发生存（RFS）有关的最佳分割值为5%。在总共374个HCC中，18.7%的病例FBXL5表达较低，与非病毒病因有关（p=0.019）。低FBXL5表达与劣质的疾病特异性生存（DSS，p=0.002）和RFS（p=0.001）相关，并且也是DSS和RFS的独立预后因子。此外，在TCGA队列中，FBXL5 mRNA水平低的病例与高的病例相比，DSS和RFS都较劣（p<0.001和p=0.002）。HCC中FBXL5表达的降低可能与不良预后有关，FBXL5可能是HCC的预后生物标志物，也是铁平衡相结合的潜在治疗靶点。版权所有©2023年，国际抗癌研究所（George J. Delinasios博士），保留所有权利。

Alteration of F-box and leucine-rich repeat protein 5 (FBXL5), an iron-sensing ubiquitin ligase, might be related with carcinogenesis of hepatocellular carcinoma (HCC), by disturbing cellular iron homeostasis. However, the clinical implications of FBXL5 expression using patient samples need to be elucidated.We collected HCC tissue samples from two institutes: Samsung Medical Center (n=259) and Hallym University Sacred Heart Hospital (n=115) and evaluated FBXL5 expression using immunohistochemistry. Using cut-off values determined by X-tile software, association between FBXL5 expression and several clinicopathological parameters was investigated. For external validation, the Cancer Genome Atlas (TCGA) cohort was used.The best cutoff value for FBXL5 IHC expression associated with recurrence-free survival (RFS) was 5%. Low FBXL5 expression was found in 18.7% of the total 374 HCCs and was associated with non-viral etiology (p=0.019). Low FBXL5 expression was related with inferior disease-specific survival (DSS, p=0.002) and RFS (p=0.001) and also was an independent prognostic factor for DSS and RFS. In addition, cases with low FBLX5 mRNA levels showed inferior DSS and RFS (p<0.001 and p=0.002, respectively) compared to high FBLX5 mRNA levels in the TCGA cohort.Down-regulation of FBXL5 expression in HCCs might be associated with poor prognosis. FBXL5 might be a prognostic biomarker of HCCs and a potential therapeutic target in conjunction with iron homeostasis.Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.