Objective: The F-box protein (FBXO) family plays a key role in the malignant progression of tumors. However, the biological functions and clinical value of the FBXO family in liver cancer remain unclear. Our study comprehensively assessed the clinical value of the FBXO family in hepatocellular carcinoma (HCC) and constructed a novel signature based on the FBXO family to predict prognosis and guide precision immunotherapy. Methods: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases were utilized to investigate the expression characteristics and prognostic value of the FBXO family in HCC. A predictive model based on the FBXO family using TCGA database; and its predictive ability was validated using the ICGC database. Further analyses revealed that this predictive model can independently predict the overall survival (OS) rate of patients with HCC. We further analyzed the association of this predictive model with signaling pathways, clinical pathological features, somatic mutations, and immune therapy responses. Finally, we validated the biological functions of cyclin F (CCNF) through in vitro experiments. Results: A predictive model involving three genes (CCNF, FBXO43, and FBXO45) was constructed, effectively identifying high and low-risk patients with differences in OS, clinicopathological characteristics, somatic mutations, and immune cell infiltration status. Additionally, knock-down of CCNF in HCC cell lines reduced cell proliferation in vitro, suggesting that CCNF may be a potential therapeutic target for HCC. Conclusions: The predictive model based on the FBXO family can effectively predict OS and the immune therapy response in HCC. Additionally, CCNF is a potential therapeutic target for HCC.

Background Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies in the world. Lamin B1 (LMNB1) is a key component of the nuclear skeleton structure. Recent studies have found that LMNB1 is overexpressed in tumor tissues and is associated with the prognosis of patients. However, the underlying mechanism remains unclear in HCC.Objective This study aims to explore the clinical significance and molecular mechanisms of LMNB1 in HCC.Methods The expression level of LMNB1 and its clinical values were analyzed with public databases, and the level of LMNB1 in HCC tissues and adjacent normal tissues was confirmed by qRT-PCR and IHC. Functional assays were conducted to explore the impact of LMNB1 knockdown on cell proliferation both in vivo and in vitro. Additionally, Genes and Genomes enrichment analysis, recovery analysis, and ChIP assays were employed to investigate its underlying molecular mechanisms. Finally, we carried out an analysis of the relationship between LMNB1 and immune cell infiltration in HCC.Results LMNB1 was found to be overexpressed in HCC and correlated with the pathological stage and unfavorable prognosis. Functional assays demonstrated that LMNB1 promotes HCC proliferation both in vitro and in vivo. Further analysis revealed that LMNB1 promotes the progression of HCC by regulating CDKN1A expression. Furthermore, the infiltration of immune cells in HCC tissues suggests a potential correlation between immune infiltration cell markers and the expression of LMNB1.Conclusions LMNB1 emerged as a promising therapeutic target and prognostic biomarker for HCC, with its expression showing a correlation with several immune infiltration cell markers.

目的 分析布-加综合征(Budd-Chiari Syndrome,BCS)及BCS合并肝癌患者血清中血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达水平及临床特征,探究影响BCS患者血清VEGF表达的相关因素.方法 收集59例BCS患者(其中下腔静脉型BCS患者12例,肝静脉型BCS患者12例,混合型BCS患者35例)、13例BCS合并肝癌患者和34例健康体检者外周血血清和临床资料,应用ELISA法检测研究对象血清VEGF表达水平并分析VEGF与临床各指标的关系.结果 BCS组血清VEGF表达水平高于健康组(P＜0.001),BCS合并肝癌组血清VEGF表达水平高于BCS组(P＜0.001);与BCS组相比,BCS合并肝癌组病程较长、副肝静脉(accessory hepatic vein,AHV)内径增宽(P＜0.05).BCS患者中,与肝静脉型相比,下腔静脉型及混合型BCS患者血清VEGF表达水平升高(P＜0.05);病程与VEGF表达呈中等强度正相关(ρ=0.558),AHV内径与VEGF表达呈较高强度正相关(ρ =0.646).结论 BCS患者血清VEGF表达水平与病程时长呈正相关关系,并与BCS类型有关.