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[多组学联合检测对高危肝癌人群机会性筛查的性能有效性]

[Multi-omics combined test performance effectiveness on opportunistic screening of high-risk liver cancer population].

作者信息

Xie C, Lin B L, Deng H, Zhang X H, Zhao Q Y, Gao Z L

机构信息

Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China.

Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China Guangdong Provincial Key Laboratory of Liver Disease, Guangzhou 510630, China.

出版信息

Zhonghua Gan Zang Bing Za Zhi. 2024 Feb 20;32(2):140-147. doi: 10.3760/cma.j.cn501113-20231125-00235.

Abstract

To validate the performance of a multi-omics combined test for early screening of high-risk liver cancer populations. 173 high-risk patients with liver cancer were prospectively screened in a real-world setting, and 164 cases were finally enrolled. B-ultrasound, alpha-fetoprotein (AFP), and HCC screens were conducted in all patients. A multi-omics early screening test was performed for liver cancer in combination with multi-gene methylation, TP53/TERT/CTNNB1 mutations, AFP, and abnormal prothrombin (PIVKA-II). Differences in rates were compared using the chi-square test, adjusted chi-square test, or Fisher's exact probability method for count data. A non-parametric rank test (Mann-Whitney) was used to compare the differences between the two groups of data. The HCCscreen detection had a sensitivity of 100% for liver cancer screening, 93.8% for liver cancer and precancerous diseases, 34.1% for positive predictive value, 99.2% for negative predictive value, and 0.89 for an area under the curve (AUC). Parallel detection of AFP, AFP+B-ultrasound, and methylation+mutation had a sensitivity/specificity and AUC of 31.3%/88.5% (AUC=0.78), 56.3%/88.2% (AUC=0.86), and 81.3%/82.4 % (AUC=0.84). At the same time, the disease severity range was significantly correlated with the methylation+mutation score, HCCscreen score, or positive detection rate (PDR). There was no significant correlation between AFP serum levels and methylation+mutation or HCCscreen scores, while there was a significant linear correlation between methylation+mutation scores and HCCscreen scores ( = 0.73,  < 0.001). In real-world settings, HCCscreen shows high sensitivity for screening opportunistic, high-risk liver cancer populations. Furthermore, it may efficaciously detect liver cancer and precancerous diseases, with superior performance to AFP and AFP+ultrasound. Hence, HCCscreen has the potential to become an effective screening tool that is superior to existing screening methods for high-risk liver cancer populations.

摘要

为验证多组学联合检测在高危肝癌人群早期筛查中的性能。在真实世界环境中对173例高危肝癌患者进行前瞻性筛查,最终纳入164例。对所有患者进行了B超、甲胎蛋白(AFP)和肝癌筛查。结合多基因甲基化、TP53/TERT/CTNNB1突变、AFP和异常凝血酶原(PIVKA-II)进行肝癌多组学早期筛查检测。对于计数数据,使用卡方检验、校正卡方检验或Fisher精确概率法比较率的差异。采用非参数秩和检验(Mann-Whitney)比较两组数据之间的差异。HCCscreen检测对肝癌筛查的灵敏度为100%,对肝癌和癌前疾病的灵敏度为93.8%,阳性预测值为34.1%,阴性预测值为99.2%,曲线下面积(AUC)为0.89。AFP、AFP+B超以及甲基化+突变的联合检测的灵敏度/特异度和AUC分别为31.3%/88.5%(AUC=0.78)、56.3%/88.2%(AUC=0.86)和81.3%/82.4%(AUC=0.84)。同时,疾病严重程度范围与甲基化+突变评分、HCCscreen评分或阳性检测率(PDR)显著相关。AFP血清水平与甲基化+突变或HCCscreen评分之间无显著相关性,而甲基化+突变评分与HCCscreen评分之间存在显著线性相关性( = 0.73, < 0.001)。在真实世界环境中,HCCscreen对机会性高危肝癌人群的筛查具有高灵敏度。此外,它可能有效地检测肝癌和癌前疾病,性能优于AFP和AFP+超声。因此,HCCscreen有潜力成为一种有效的筛查工具,优于现有的高危肝癌人群筛查方法。

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