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乙型肝炎病毒相关性肝细胞癌中 WNT 家族基因表达的诊断和预后价值。

Diagnostic and prognostic value of WNT family gene expression in hepatitis B virus‑related hepatocellular carcinoma.

机构信息

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.

Department of Colorectal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.

出版信息

Oncol Rep. 2019 Sep;42(3):895-910. doi: 10.3892/or.2019.7224. Epub 2019 Jul 5.

Abstract

The aim of the present study was to investigate the diagnostic and prognostic value of Wingless‑type MMTV integration site (WNT) gene family expression in patients with hepatitis B virus (HBV)‑related hepatocellular carcinoma (HCC). The clinical data of the patients and gene expression levels were downloaded from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Receiver operating characteristic curve analysis was used to investigate the diagnostic value of WNT genes. Cox proportional hazard regression analysis and Kaplan‑Meier survival analysis were performed to evaluate the association of WNT gene expression level with overall survival (OS) and recurrence‑free survival (RFS). A nomogram was constructed for the prediction of prognosis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Diagnostic receiver operating characteristic curve analysis suggested that WNT2 had a high diagnostic value, with an area under the curve (AUC) of >0.800 (P<0.0001, AUC=0.810, 95% CI: 0.767‑0.852). Survival analysis indicated that the expression level of WNT1 was significantly associated with OS and RFS (adjusted P=0.033, adjusted HR=0.607, 95% CI: 0.384‑0.960; and adjusted P=0.007, adjusted HR=0.592, 95% CI: 0.404‑0.868, respectively). In the TCGA validation cohort, we also observed that WNT2 was significantly differentially expressed between HCC tissues and adjacent non‑tumor tissues, and WNT1 was associated with both the OS and RFS of HCC. Therefore, through the GSE14520 HBV‑related HCC cohort we concluded that WNT2 may serve as a diagnostic biomarker and WNT1 may serve as a prognostic biomarker. These results may also be extended to TCGA HCC verification cohort.

摘要

本研究旨在探讨 Wingless 型 MMTV 整合位点(WNT)基因家族在乙型肝炎病毒(HBV)相关肝细胞癌(HCC)患者中的诊断和预后价值。从基因表达综合数据库(GEO)和癌症基因组图谱(TCGA)数据库中下载患者的临床数据和基因表达水平。采用受试者工作特征曲线分析探讨 WNT 基因的诊断价值。采用Cox 比例风险回归分析和 Kaplan-Meier 生存分析评估 WNT 基因表达水平与总生存期(OS)和无复发生存期(RFS)的相关性。构建列线图预测预后。计算危险比(HRs)和 95%置信区间(CIs)。诊断受试者工作特征曲线分析表明,WNT2 具有较高的诊断价值,曲线下面积(AUC)>0.800(P<0.0001,AUC=0.810,95%CI:0.767-0.852)。生存分析表明,WNT1 的表达水平与 OS 和 RFS 显著相关(调整 P=0.033,调整 HR=0.607,95%CI:0.384-0.960;调整 P=0.007,调整 HR=0.592,95%CI:0.404-0.868)。在 TCGA 验证队列中,我们还观察到 WNT2 在 HCC 组织和相邻非肿瘤组织之间的表达存在显著差异,WNT1 与 HCC 的 OS 和 RFS 均相关。因此,通过 GSE14520 HBV 相关 HCC 队列,我们得出结论,WNT2 可能作为诊断生物标志物,WNT1 可能作为预后生物标志物。这些结果也可能扩展到 TCGA HCC 验证队列。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ca1/6667889/f339cb331b2c/or-42-03-0895-g00.jpg

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