Liu Yue, Fu Bidong, Yu Zichuan, Song Gelin, Zeng Hong, Gong Yiyang, Ding Yongqi, Huang Da
Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330000, People's Republic of China.
Second College of Clinical Medicine, Nanchang University, Nanchang, Jiangxi Province, 330000, People's Republic of China.
J Hepatocell Carcinoma. 2022 May 31;9:497-516. doi: 10.2147/JHC.S363862. eCollection 2022.
Hepatocellular carcinoma (HCC) is a malignancy with high incidence, but its prognosis is not optimistic. KRBA1 is a member of the KRAB family and participates in the regulation of gene transcription. However, no studies have focused on the role of KRBA1 in HCC.
In this study, we first analyzed the expression of KRBA1 in HCC using TCGA and ICGC databases and validated by Immunohistochemistry in clinical HCC samples. The Wilcoxon rank-sum test was used to determine the relationship between KRBA1 expression and clinicopathological features. Subsequently, we used Kaplan-Meier online website analysis and Cox regression model to predict the prognostic value of KRBA1 in HCC patients. Furthermore, the functions of KRBA1 were identified by enrichment analysis. TIMER and GSCALite were used to investigate the relationship between KRBA1 expression in HCC and immune infiltration and drug targets, respectively. Finally, the relationship between KRBA1 expression and m6A modification in HCC was analyzed using the TCGA and ICGA datasets.
The results showed that KRBA1 was upregulated in HCC and was associated with many clinicopathological features. High KRBA1 causes poor overall survival and may be an independent risk factor for HCC. KRBA1 tends to be hypermethylated and associated with poor prognosis in HCC compared with normal tissues. Enrichment analysis indicates that KRBA1 is associated with cell cycle and immune processes, and TIMER analysis shows that KRBA1 expression is associated with infiltration levels and immune characteristics of various immune cells. Silenced KRBA1 evidently reduced three chemokine expression in HCC cells. Drug sensitivity analysis showed that KRBA1 was sensitive to 39 drug small molecules. KRBA1 showed a strong positive correlation with five m6A related genes.
KRBA1 is a prognostic biomarker associated with HCC immunity and m6a modification, serving as an effective target for the diagnosis and treatment of HCC.
肝细胞癌（HCC）是一种发病率很高的恶性肿瘤，但其预后并不乐观。KRBA1是KRAB家族的成员，参与基因转录的调控。然而，尚无研究关注KRBA1在HCC中的作用。
在本研究中，我们首先使用TCGA和ICGC数据库分析了KRBA1在HCC中的表达，并通过免疫组织化学在临床HCC样本中进行了验证。采用Wilcoxon秩和检验来确定KRBA1表达与临床病理特征之间的关系。随后，我们使用Kaplan-Meier在线网站分析和Cox回归模型来预测KRBA1在HCC患者中的预后价值。此外，通过富集分析确定KRBA1的功能。分别使用TIMER和GSCALite研究HCC中KRBA1表达与免疫浸润和药物靶点之间的关系。最后，使用TCGA和ICGA数据集分析HCC中KRBA1表达与m6A修饰之间的关系。
结果显示，KRBA1在HCC中上调，并与许多临床病理特征相关。KRBA1高表达导致总体生存率较差，可能是HCC的独立危险因素。与正常组织相比，KRBA1在HCC中倾向于高甲基化且与预后不良相关。富集分析表明，KRBA1与细胞周期和免疫过程相关，TIMER分析表明KRBA1表达与各种免疫细胞的浸润水平和免疫特征相关。沉默KRBA1明显降低了HCC细胞中三种趋化因子的表达。药物敏感性分析表明，KRBA1对39种药物小分子敏感。KRBA1与五个m6A相关基因呈强正相关。
KRBA1是一种与HCC免疫和m6A修饰相关的预后生物标志物，可作为HCC诊断和治疗的有效靶点。
