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血浆无细胞腺瘤性结肠息肉病基因启动子甲基化作为肝细胞癌的预后生物标志物。

Plasma Cell-Free Adenomatous Polyposis Coli Gene Promoter Methylation as a Prognostic Biomarker for Hepatocellular Carcinoma.

机构信息

Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan,

Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan,

出版信息

Oncology. 2024;102(11):935-943. doi: 10.1159/000538455. Epub 2024 Mar 25.

Abstract

INTRODUCTION

Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide. Lack of biomarkers for follow-up after treatment is a clinical challenge. DNA methylation has been proposed to be a potential biomarker in HCC. However, there is still a lack of evidence of its clinical use. This study aimed to evaluate the value of using plasma Adenomatous Polyposis Coli promoter methylation level (APC-MET) as a potential biomarker in HCC treatment.

METHOD

A total of 96 patients with HCC at BCLC stage B who underwent local tumor ablation treatment were prospectively included in this study. APC-MET was examined in the plasma of each patient before and 1 month after treatment. The prediction value of APC-MET for survival outcome and disease status after treatment was analyzed and adjusted with alpha-fetoprotein and protein induced by vitamin K absence-II using Cox regression analysis.

RESULTS

Univariate Cox regression analysis showed preoperative APC-MET >0 (HR, 2.9, 95% CI: 1.05-8.05, p = 0.041) and postoperative APC-MET >0 (HR, 3.47, 95% CI: 1.16-10.4, p = 0.026) were both predictors of death, and preoperative APC-MET >0 was a predictor of disease progression after treatment (HR, 2.04, 95% CI: 1.21-3.44, p = 0.007). In multivariate models, preoperative APC-MET >0 was a significant predictor of disease progression after adjusting with the other two traditional biomarkers (HR, 1.82, 95% CI: 1.05-3.17, p = 0.034).

CONCLUSIONS

Hypermethylation of APC promoter appears to be a potential biomarker that could predict patient survival and disease progression outcomes in patients with intermediate-stage HCC after local ablation treatment.

摘要

简介

肝细胞癌(HCC)是全球癌症死亡的主要原因。缺乏治疗后随访的生物标志物是临床面临的挑战。DNA 甲基化已被提议作为 HCC 的潜在生物标志物。然而,其临床应用仍缺乏证据。本研究旨在评估使用血浆腺瘤性结肠息肉病(APC)启动子甲基化水平(APC-MET)作为 HCC 治疗后潜在生物标志物的价值。

方法

本研究前瞻性纳入 96 例 BCLC 分期 B 的 HCC 局部肿瘤消融治疗患者。在治疗前后,每位患者的血浆中均检测 APC-MET。采用 Cox 回归分析,分析并调整甲胎蛋白(AFP)和维生素 K 缺乏诱导蛋白-II(PIVKA-II)后,APC-MET 对生存结局和治疗后疾病状态的预测价值。

结果

单因素 Cox 回归分析显示,术前 APC-MET>0(HR,2.9,95%CI:1.05-8.05,p=0.041)和术后 APC-MET>0(HR,3.47,95%CI:1.16-10.4,p=0.026)均是死亡的预测因素,术前 APC-MET>0 是治疗后疾病进展的预测因素(HR,2.04,95%CI:1.21-3.44,p=0.007)。在多因素模型中,调整其他两个传统生物标志物后,术前 APC-MET>0 是疾病进展的显著预测因素(HR,1.82,95%CI:1.05-3.17,p=0.034)。

结论

APC 启动子高甲基化似乎是一种潜在的生物标志物,可预测局部消融治疗后中期 HCC 患者的生存和疾病进展结局。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0a2/11548096/2d5b0f08e5c8/ocl-2024-0102-0011-538455_F01.jpg

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