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RAD51AP1 在与肝癌患者总生存和无病生存相关的肿瘤组织中的致癌作用。

Oncogenic Roles of RAD51AP1 in Tumor Tissues Related to Overall Survival and Disease-Free Survival in Hepatocellular Carcinoma.

机构信息

Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

Department of Integrative Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

出版信息

Cancer Control. 2020 Jan-Dec;27(1):1073274820977149. doi: 10.1177/1073274820977149.

DOI:10.1177/1073274820977149
PMID:33269607
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8480365/
Abstract

OBJECTIVE

This study aimed to investigate the associations between RAD51AP1 and the outcomes of hepatocellular carcinoma (HCC).

METHODS

RAD51AP1 expression levels were compared in Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets. The Liver Hepatocellular Carcinoma (TCGA, Provisional) and GSE36376 datasets were used for survival analysis. RAD51AP1 associations with clinicopathological features were determined with the GSE36376 dataset.

RESULTS

RAD51AP1 mRNA expression was significantly upregulated in advanced liver fibrosis samples (S3-4 vs. S0-2 and G3-4 vs. G0-2) from hepatitis B virus (HBV)-related liver fibrosis patients and in tumor tissues and peripheral blood mononuclear cells (PBMCs) from HCC patients (all < 0.05). HCC patients with high RAD51AP1 expression had significantly worse overall survival (OS) and disease-free survival (DFS) than those with low RAD51AP1 expression ( = 0.0034 and = 0.0012, respectively) in the TCGA dataset, and these findings were validated with the GSE36376 dataset ( = 0.0074 and = 0.0003, respectively). A Cox regression model indicated that RAD51AP1 was a risk factor for OS and DFS in HCC patients in GSE36376 (HR = 1.54, 95% CI = 1.02-2.32, = 0.04 and HR = 1.71, 95% CI = 1.22-2.39, = 0.002, respectively). Moreover, RAD51AP1 mRNA expression increased gradually with increasing tumor stage, including stratification by American Joint Committee on Cancer (AJCC) stages, Barcelona Clinic Liver Cancer (BCLC) stages and Edmondson grades. In addition, RAD51AP1 was overexpressed in HCC patients with intrahepatic metastasis, major portal vein invasion, vascular invasion and/or an alpha-fetoprotein (AFP) level > 300 ng/ml.

CONCLUSIONS

Contributing to an advanced tumor stage, intrahepatic metastasis, vascular invasion and AFP level elevation, RAD51AP1 upregulation was significantly associated with OS and DFS in HCC patients.

摘要

目的

本研究旨在探讨 RAD51AP1 与肝细胞癌(HCC)结局之间的关系。

方法

在基因表达综合数据库(GEO)和癌症基因组图谱(TCGA)数据库中比较 RAD51AP1 的表达水平。使用 Liver Hepatocellular Carcinoma(TCGA,临时)和 GSE36376 数据集进行生存分析。使用 GSE36376 数据集确定 RAD51AP1 与临床病理特征的关联。

结果

乙型肝炎病毒(HBV)相关肝纤维化患者的晚期肝纤维化样本(S3-4 与 S0-2 和 G3-4 与 G0-2)和 HCC 患者的肿瘤组织和外周血单核细胞(PBMC)中,RAD51AP1 mRNA 表达显著上调(均<0.05)。TCGA 数据库中,RAD51AP1 高表达的 HCC 患者的总生存期(OS)和无病生存期(DFS)明显低于 RAD51AP1 低表达的患者(=0.0034 和=0.0012,分别),GSE36376 数据集的结果得到了验证(=0.0074 和=0.0003,分别)。Cox 回归模型表明,在 GSE36376 中,RAD51AP1 是 HCC 患者 OS 和 DFS 的危险因素(HR=1.54,95%CI=1.02-2.32,=0.04 和 HR=1.71,95%CI=1.22-2.39,=0.002,分别)。此外,RAD51AP1 mRNA 表达随着肿瘤分期的增加而逐渐升高,包括根据美国癌症联合委员会(AJCC)分期、巴塞罗那临床肝癌(BCLC)分期和 Edmondson 分级进行分层。此外,RAD51AP1 在 HCC 患者中呈高表达,这些患者存在肝内转移、主门静脉侵犯、血管侵犯和/或甲胎蛋白(AFP)水平>300ng/ml。

结论

RAD51AP1 的上调与 HCC 患者的 OS 和 DFS 显著相关,这与肿瘤分期进展、肝内转移、血管侵犯和 AFP 水平升高有关。

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