F-Box 和富含亮氨酸重复蛋白 5（FBXL5）表达缺失与根治性切除术后肝细胞癌患者的不良生存相关：一项两机构研究。
Loss of F-Box and Leucine Rich Repeat Protein 5 (FBXL5) Expression Is Associated With Poor Survival in Patients With Hepatocellular Carcinoma After Curative Resection: A Two-institute Study.
机构信息
Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea.
出版信息
Cancer Genomics Proteomics. 2023 May-Jun;20(3):298-307. doi: 10.21873/cgp.20382.
BACKGROUND/AIM: 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.
PATIENTS AND METHODS
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.
RESULTS
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.
CONCLUSION
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.
背景/目的：铁感应泛素连接酶 F-box 和亮氨酸丰富重复蛋白 5（FBXL5）的改变可能通过扰乱细胞内铁稳态与肝细胞癌（HCC）的癌变有关。然而，使用患者样本评估 FBXL5 表达的临床意义仍需要阐明。
患者和方法
我们从两个机构收集 HCC 组织样本：三星医疗中心（n=259）和翰林大学圣心医院（n=115），并使用免疫组织化学评估 FBXL5 的表达。使用 X-tile 软件确定的截止值，研究 FBXL5 表达与几种临床病理参数之间的关联。为了外部验证，使用癌症基因组图谱（TCGA）队列。
结果
与无复发生存率（RFS）相关的 FBXL5 IHC 表达最佳截断值为 5%。在总共 374 例 HCC 中，低 FBXL5 表达占 18.7%，与非病毒性病因有关（p=0.019）。低 FBXL5 表达与较差的疾病特异性生存率（DSS，p=0.002）和 RFS（p=0.001）相关，也是 DSS 和 RFS 的独立预后因素。此外，在 TCGA 队列中，低 FBLX5 mRNA 水平的病例与高 FBLX5 mRNA 水平的病例相比，DSS 和 RFS 较差（p<0.001 和 p=0.002）。
结论
HCC 中 FBXL5 表达的下调可能与预后不良有关。FBXL5 可能是 HCC 的预后生物标志物，也是与铁稳态结合的潜在治疗靶点。
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