小 GTP 酶 Ran 及其甲基化在肝细胞癌中的预后潜力。

Prognostic potential of the small GTPase Ran and its methylation in hepatocellular carcinoma.

机构信息

Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250000, China.

Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250000, China; Shenzhen Research Institute of Shandong University, Shenzhen 518000, China; Institute of Hepatology, Shandong University, Jinan 250000, China.

出版信息

Hepatobiliary Pancreat Dis Int. 2022 Jun;21(3):248-256. doi: 10.1016/j.hbpd.2022.03.011. Epub 2022 Mar 22.

DOI:10.1016/j.hbpd.2022.03.011

PMID:35367146

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality. The prognostic significance of Ran, a member of Ras superfamily, remains unclear in HCC patients.

METHODS

Based on The Cancer Genome Atlas (TCGA) database and Tumor Immune Estimation Resource (TIMER), we analyzed the correlations among Ran expression, promoter methylation and immune cell infiltration. We also investigated the Ran expression levels in HCC tissues and normal tissues by using quantitative real-time PCR.

RESULTS

Ran mRNA expression was significantly increased in HCC tissues compared with the normal tissues (P < 0.001). Time-dependent receiver operating characteristic (ROC) curves showed that Ran expression had predictive value of the 1-, 3- and 5-year overall survival for HCC patients, and the areas under the curves (AUC) were 0.747, 0.634 and 0.704, respectively. Cox regression analysis showed that Ran expression was an independent prognostic factor for HCC patients (HR = 1.492, 95% CI: 1.129-1.971, P = 0.005). We also found a negative relationship between Ran mRNA expression and its promoter methylation (r = -0.36, P < 0.001). High Ran expression and promoter hypomethylation predicted worse overall survival and progression-free survival (P < 0.05) and were involved in the progression of HCC. Ran expression exhibited significant correlations with immune infiltrates and prognostic immune-related genes.

CONCLUSIONS

The present study provides further insight into the prognosis of HCC, and Ran could serve as a biomarker for predicting the survival of HCC patients.

摘要

背景

肝细胞癌（HCC）是一种常见的恶性肿瘤，死亡率高。 Ras 超家族成员 Ran 在 HCC 患者中的预后意义尚不清楚。

方法

基于癌症基因组图谱（TCGA）数据库和肿瘤免疫估计资源（TIMER），我们分析了 Ran 表达、启动子甲基化与免疫细胞浸润之间的相关性。我们还通过实时定量 PCR 检测 HCC 组织和正常组织中的 Ran 表达水平。

结果

HCC 组织中 Ran mRNA 表达明显高于正常组织（P<0.001）。时间依赖性受试者工作特征（ROC）曲线表明，Ran 表达对 HCC 患者的 1 年、3 年和 5 年总生存率具有预测价值，曲线下面积（AUC）分别为 0.747、0.634 和 0.704。Cox 回归分析显示，Ran 表达是 HCC 患者的独立预后因素（HR=1.492，95%CI：1.129-1.971，P=0.005）。我们还发现 Ran mRNA 表达与其启动子甲基化呈负相关（r=-0.36，P<0.001）。高 Ran 表达和启动子低甲基化预示着总生存率和无进展生存率较差（P<0.05），并参与了 HCC 的进展。Ran 表达与免疫浸润和预后免疫相关基因显著相关。