Zhang Jing, Yang Gang, Li Qiang, Xie Fei
Department of Gastroenterology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.
Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.
Oncol Lett. 2021 Feb;21(2):92. doi: 10.3892/ol.2020.12353. Epub 2020 Dec 6.
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.
肝细胞癌(HCC)是全球第六大常见癌症,也是癌症相关死亡的第三大常见原因。肝切除术和肝移植是早期HCC的主要治疗方法。晚期HCC的免疫治疗和靶向治疗越来越普遍;然而,它们的临床益处有限。因此,确定晚期HCC的新治疗靶点仍然至关重要。纤维蛋白原(FBL)是一种重要的核仁蛋白,可催化核糖体RNA的2'-O-甲基化。最近,实验数据表明FBL可影响乳腺癌进展。然而,FBL表达与HCC之间的关联尚不清楚。在本研究中,使用UALCAN数据库评估HCC中FBL mRNA的表达。对139例HCC患者进行免疫组织化学分析以检测FBL蛋白表达。此外,使用UALCAN、注释、可视化和综合发现数据库、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Cox比例风险回归模型分析数据。结果表明,与癌旁组织相比,肿瘤组织中FBL表达明显更高。此外,高FBL表达与HCC中的肿瘤直径和晚期TNM分期显著相关。高FBL表达还预示着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可能受甲基化修饰调控。此外,使用基因本体数据库进行的功能注释分析表明,FBL相关基因主要富集于DNA修复和增殖相关的细胞信号通路。值得注意的是,高FBL表达意味着肿瘤直径更大、肿瘤分期更晚且预后较差。综上所述,本研究结果表明FBL可能是HCC治疗的潜在靶点。