Combination Assay of Methylated HOXA1 with Tumor Markers Shows High Sensitivity for Detection of Early-Stage Hepatocellular Carcinoma

IF 11.6 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Liver Cancer Pub Date : 2024-02-14 DOI:10.1159/000536211

Yuki Kunimune, Yutaka Suehiro, I. Saeki, Yurika Yamauchi, N. Tanabe, Toshihiko Matsumoto, S. Higaki, Ikuei Fujii, Chieko Suzuki, N. Okayama, Mitsuaki Nishioka, Kiyoshi Ichihara, Hiroaki Nagano, Isao Sakaida, T. Takami, Takahiro Yamasaki

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引用次数: 0

Abstract

Introduction: Patients with hepatitis virus-related hepatocellular carcinoma (viral HCC) are decreasing as hepatitis control improves, but those with non-viral-related HCC (non-viral HCC) are increasing in Japan. No established surveillance system exists for patients with non-viral HCC, so they are often diagnosed at an advanced stage. To address this, we performed this study. Methods: We collected serum samples from 516 participants (154 healthy subjects, 93 chronic liver disease [CLD] patients without HCC, and 269 HCC patients). Participants were divided into a control group comprising healthy subjects and patients with CLD and an HCC group. We evaluated serum methylated HOXA1 (m-HOXA1) copy numbers using modified combined restriction digital PCR (CORD) assay (1-step CORD assay). We assessed diagnostic performance of m-HOXA1 compared to HCC tumor markers alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) and created a novel index to improve HCC prediction. Results: Serum m-HOXA1 level was significantly higher in each HCC stage group versus the control group. Its sensitivity was 69.1% and specificity was 78.5% for diagnosing HCC. The area under the curve (AUC) of m-HOXA1 was superior to that of AFP and equal to that of DCP. Multivariate logistic regression analysis revealed independent contributions of m-HOXA1, DCP, and AFP, in that order of strength, to diagnose HCC after adjustment for age and sex. We designated the predictive probability of HCC based on the regression model as the ASDAm-H1 (Age, Sex, DCP, AFP, and m-HOXA1) index. Its diagnostic accuracy was 0.96 by AUC with a sensitivity of 86.2% and specificity of 93.9%. Sensitivity was identical for viral and non-viral HCCs. When limited to early-stage HCC, sensitivity of the ASDAm-H1 index was 76.3%. Conclusions: We showed distinguished performance of the ASDAm-H1 index to detect viral and non-viral HCC, even at an early stage. This index might have potential as a non-viral HCC surveillance system.

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甲基化 HOXA1 与肿瘤标志物的联合检测显示出检测早期肝细胞癌的高灵敏度

简介：随着肝炎控制工作的改善，与肝炎病毒相关的肝细胞癌（病毒性 HCC）患者正在减少，但在日本，与非病毒相关的 HCC（非病毒性 HCC）患者正在增加。目前还没有针对非病毒性 HCC 患者的监测系统，因此他们往往在晚期才被诊断出来。为了解决这个问题，我们进行了这项研究。研究方法我们收集了 516 名参与者（154 名健康人、93 名无 HCC 的慢性肝病 [CLD] 患者和 269 名 HCC 患者）的血清样本。参与者被分为由健康人和慢性肝病患者组成的对照组和 HCC 组。我们使用改良的联合限制性数字 PCR（CORD）检测法（一步式 CORD 检测法）评估了血清甲基化 HOXA1（m-HOXA1）的拷贝数。与 HCC 肿瘤标志物甲胎蛋白（AFP）和去γ-羧基凝血酶原（DCP）相比，我们评估了 m-HOXA1 的诊断性能，并创建了一个新的指数来改进 HCC 预测。结果血清 m-HOXA1 水平在各 HCC 分期组均明显高于对照组。其诊断 HCC 的敏感性为 69.1%，特异性为 78.5%。m-HOXA1 的曲线下面积（AUC）优于 AFP，与 DCP 相等。多变量逻辑回归分析显示，在对年龄和性别进行调整后，m-HOXA1、DCP 和 AFP 对 HCC 诊断的贡献依次独立。我们将基于回归模型的 HCC 预测概率命名为 ASDAm-H1（年龄、性别、DCP、AFP 和 m-HOXA1）指数。根据 AUC 值，其诊断准确率为 0.96，灵敏度为 86.2%，特异性为 93.9%。病毒性和非病毒性 HCC 的灵敏度相同。如果仅限于早期 HCC，ASDAm-H1 指数的灵敏度为 76.3%。结论：我们发现 ASDAm-H1 指数在检测病毒性和非病毒性 HCC 方面表现出色，即使是在早期阶段。该指数可能具有作为非病毒性 HCC 监测系统的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Liver Cancer Medicine-Oncology

CiteScore

20.80

自引率

7.20%

发文量

审稿时长

16 weeks

期刊介绍： Liver Cancer is a journal that serves the international community of researchers and clinicians by providing a platform for research results related to the causes, mechanisms, and therapy of liver cancer. It focuses on molecular carcinogenesis, prevention, surveillance, diagnosis, and treatment, including molecular targeted therapy. The journal publishes clinical and translational research in the field of liver cancer in both humans and experimental models. It publishes original and review articles and has an Impact Factor of 13.8. The journal is indexed and abstracted in various platforms including PubMed, PubMed Central, Web of Science, Science Citation Index, Science Citation Index Expanded, Google Scholar, DOAJ, Chemical Abstracts Service, Scopus, Embase, Pathway Studio, and WorldCat.

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