Increased fibrillarin expression is associated with tumor progression and an unfavorable prognosis in hepatocellular carcinoma.
Increased fibrillarin expression is associated with tumor progression and an unfavorable prognosis in hepatocellular carcinoma.
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原纤维蛋白表达增加与肝细胞癌的肿瘤进展和不良预后相关。
DOI：
10.3892/ol.2020.12353
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发表时间：
2021-03
期刊：
影响因子：
2.9
通讯作者：
Xie F
中科院分区：
文献类型：
--
作者：
Zhang J;Yang G;Li Q;Xie F
肝细胞癌（HCC）是世界范围内第六大常见癌症和第三大常见癌症相关死亡原因。肝切除和肝移植是早期肝癌的主要治疗手段。免疫治疗和靶向治疗晚期肝癌已越来越受欢迎，但其临床获益有限。因此，晚期HCC的新治疗靶点的确定仍然是必要的。原纤蛋白（Fibrillarin，FBL）是一种重要的核仁蛋白，催化核糖体RNA的2′-O-甲基化。最近，实验数据表明，FBL可以影响乳腺癌的进展。然而，FBL表达和HCC之间的关联仍然是已知的。在本研究中，使用UALCAN数据库来评估HCC中FBL mRNA的表达。应用免疫组化方法检测139例HCC组织中FBL蛋白的表达。此外，使用UALCAN、注释、可视化和集成发现数据库、cBioportal和TargetScan数据库进行生物信息学分析。使用Kaplan-Meier曲线和对数秩检验以及考克斯比例风险回归模型分析数据。结果表明，FBL在肿瘤组织中的表达显著高于癌旁组织。FBL的高表达与肿瘤直径和TNM分期密切相关。FBL高表达还可预测HCC患者的总生存时间和无病生存时间较短。生物信息学分析表明，FBL可能受到甲基化修饰的调控。此外，使用Gene Ontology数据库进行的功能注释分析表明，FBL相关基因主要富集在DNA修复和增殖相关的细胞信号传导途径中。值得注意的是，FBL高表达意味着肿瘤直径更大，肿瘤分期更高，预后更差。总之，本研究的结果表明，FBL可能是肝癌治疗的潜在靶点。
Hepatocellular carcinoma (HCC) is the sixth most common cancer and third most common cause of cancer-associated mortality worldwide. Hepatectomy and liver transplantation are the main treatments for early HCC. Immunotherapy and targeted therapy for advanced HCC have become increasingly popular; however, their clinical benefits are limited. Thus, identification of novel therapeutic targets for advanced HCC remains essential. Fibrillarin (FBL) is an essential nucleolar protein that catalyzes the 2′-O-methylation of ribosomal RNAs. Recently, experimental data have suggested that FBL can influence breast-cancer progression. However, the association between FBL expression and HCC remains known. In the present study, the UALCAN database was used to assess FBL mRNA expression in HCC. Immunohistochemistry analysis was performed to detect FBL protein expression in 139 patients with HCC. In addition, bioinformatic analysis was performed using the UALCAN, the Database for Annotation, Visualization and Integrated Discovery, cBioportal and TargetScan databases. Data were analyzed using Kaplan-Meier curves and the log-rank test, and a Cox proportional hazards regression model. The results demonstrated that FBL expression was significantly higher in tumor tissues compared with para-tumor tissues. Furthermore, high FBL expression was significantly associated with tumor diameter and advanced TNM stage in HCC. High FBL expression also predicted a shorter overall survival time and disease-free survival time in patients with HCC. Bioinformatics analysis demonstrated that FBL may be regulated by methylation modification. In addition, analyses of functional annotations using the Gene Ontology database indicated that FBL-related genes were predominantly enriched in DNA repair and proliferation-related cell-signaling pathways. Notably, high FBL expression signified larger tumor diameter, advanced tumor stage and a poor prognosis. Taken together, the results of the present study suggest that FBL may be a potential target for HCC treatment.
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DOI：
10.1042/bcj20160930
发表时间：
2017-02-01
期刊：
The Biochemical journal
影响因子：
--
作者：
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通讯作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
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影响因子：
64.5
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Hu H
影响因子：
30.8
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通讯作者：
Bristow, Robert G.