摘要
目的 拟验证一项多组学联合检测在肝癌高危人群进行肝癌早筛的性能.方法 在真实世界环境下前瞻性筛选173例肝癌高危患者,最后入组164例患者.所有患者均行B超、甲胎蛋白(AFP)和HCCscreen检测.HCCscreen检测是一项合并多基因甲基化、TP53/TERT/CTNNB1突变、AFP和异常凝血酶原(PIVKA-Ⅱ)的多组学肝癌早筛检测.计数资料使用x2检验、校正x2检验或Fisher精确概率法比较率的差异;等级资料使用非参数检验(Mann-Whitney)法比较两组数据间的差异.结果 HCCscreen检测对肝癌的筛查灵敏度为100％,对肝癌及癌前疾病的筛查灵敏度为93.8％,阳性预测值34.1％,阴性预测值99.2％,曲线下面积(AUC)为0.89.平行检测的AFP、AFP+B超和甲基化+突变的灵敏度/特异度及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,疾病严重程度与甲基化+突变评分、HCCscreen评分或阳性检出率存在显著相关性.虽然AFP血清水平与甲基化+突变或HCCscreen评分之间没有显著相关性,但甲基化+突变评分与HCCscreen评分之间存在显著的线性相关性(r=0.73,P＜0.001).结论 在真实世界机会性筛查条件下,HCCscreen显示出对肝癌高危人群筛查高灵敏度,可有效发现肝癌及癌前疾病,其表现优于AFP及AFP+B超.HCCscreen有潜力成为优于现有筛查方法的肝癌高危人群的有效筛查工具.
Abstract
Objective To validate the performance of a multi-omics combined test for early screening of high-risk liver cancer populations.Methods 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.Results 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(r=0.73,P＜0.001).Conclusion 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.
基金项目
"十三五"国家科技重大专项(2018ZX10302204)
国家自然科学基金(82170612)
国家自然科学基金(81472259)
国家自然科学基金(81570539)
维普
万方数据