五种血清生物标志物在肝细胞癌早期诊断中的直接比较。

StephenW

Cancer Manag Res. 2018 Jul 10;10:1947-1958. doi: 10.2147/CMAR.S167036. eCollection 2018.
Direct comparison of five serum biomarkers in early diagnosis of hepatocellular carcinoma.
Chen H#1, Zhang Y#1,2, Li S#3, Li N1, Chen Y4, Zhang B3, Qu C1, Ding H4, Huang J3,5, Dai M1.
Author information

1
    National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, [email protected].
2
    Office of Scientific Research, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.
3
    Liver Research Center, Experimental Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing, China, [email protected].
4
    Department of Gastrointestinal and Hepatology, Beijing You' An Hospital Affiliated to Capital Medical University, Beijing, China.
5
    National Clinical Research Center of Digestive Diseases, Beijing, China, [email protected].
#
    Contributed equally

Abstract
Background:

Although a number of serum biomarkers for detection of hepatocellular carcinoma (HCC) have been explored, their exact diagnostic value remains unclear. We aimed to conduct a direct comparison of five representative serum biomarkers for detecting HCC and to derive multi-marker prediction algorithms.
Patients and methods:

In total, 846 patients were recruited from three hospitals in China, including 202 HCC patients, 226 liver cirrhosis patients, 215 chronic hepatitis B virus-infected patients, and 203 healthy volunteers. Serum levels of alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP (AFP-L3), des-gamma-carboxyprothrombin (DCP), squamous cell carcinoma antigen, and centromere protein F autoantibody were measured by ELISA. The diagnostic performances of individual biomarkers and multi-marker combinations were evaluated by receiver operating characteristics analysis. The bootstrapping method was adopted to adjust for potential overfitting of all diagnostic indicators.
Results:

DCP exhibited the best diagnostic performance, with areas under the curve (AUC) for detecting HCC of 0.82 (95% CI 0.64-0.80) and sensitivity of 65.2% (95% CI 63.3-82.1%) at 90% specificity. Of note, DCP showed similar diagnostic efficacy for detecting AFP-positive and AFP-negative HCC. After a comprehensive search for multi-marker combinations, a two-marker prediction algorithm including AFP and DCP was constructed and yielded an AUC of 0.87 (95% CI 0.68-0.84) for detecting HCC. In addition, the combination showed good ability in discriminating early-stage HCC and decompensated liver cirrhosis, with an AUC of 0.81 (95% CI 0.75-0.86).
Conclusion:

DCP could be a complementary biomarker in the early diagnosis of HCC. The constructed multi-marker prediction algorithms could contribute toward distinguishing HCC from non-malignant chronic liver diseases.
KEYWORDS:

early detection; liver cirrhosis; prediction model

PMID:
    30022853
PMCID:
    PMC6044429
DOI:
    10.2147/CMAR.S167036

StephenW

巨蟹座Manag Res。 2018年7月10日; 10：1947-1958。 doi：10.2147 / CMAR.S167036。 eCollection 2018。
五种血清生物标志物在肝细胞癌早期诊断中的直接比较。
Chen H＃1，Zhang Y＃1,2，Li S＃3，Li N1，Chen Y4，Zhang B3，Qu C1，Ding H4，Huang J3,5，Dai M1。
作者信息

1
    中国医学科学院北京协和医学院肿瘤/肿瘤医院国家癌症中心/国家临床研究中心，北京，daimin2002 @ hotmail.com。
2
    首都医科大学附属北京妇产医院科研办公室，北京
3
    首都医科大学附属北京友谊医院实验中心肝脏研究中心，北京市肝硬化转化医学重点实验室，北京，huangj1966 @ hotmail.com。
4
    北京首都医科​​大学附属北京佑安医院胃肠与肝脏科，北京
五
    国家消化病临床研究中心，北京，huangj1966 @ hotmail.com。
＃
    贡献一致

抽象
背景：

尽管已经探索了许多用于检测肝细胞癌（HCC）的血清生物标志物，但它们的确切诊断价值仍不清楚。我们的目的是对五种代表性血清生物标志物进行直接比较，以检测HCC并推导出多标志物预测算法。
患者和方法：

共有846名患者从中国三家医院招募，其中包括202名HCC患者，226名肝硬化患者，215名慢性乙型肝炎病毒感染患者和203名健康志愿者。通过ELISA测量血清中甲胎蛋白（AFP），晶状体凝集素反应性AFP（AFP-L3），去γ-羧基凝血酶原（DCP），鳞状细胞癌抗原和着丝粒蛋白F自身抗体的水平。通过接受者操作特征分析评估各个生物标志物和多标志物组合的诊断性能。采用自举方法来调整所有诊断指标的潜在过度拟合。
结果：

DCP表现出最佳的诊断性能，其中检测HCC的曲线下面积（AUC）为0.82（95％CI 0.64-0.80），灵敏度为65.2％（95％CI 63.3-82.1％），特异性为90％。值得注意的是，DCP显示出用于检测AFP阳性和AFP阴性HCC的类似诊断功效。在全面搜索多标记物组合后，构建了包括AFP和DCP的双标记物预测算法，并且产生了0.87（95％CI 0.68-0.84）的AUC用于检测HCC。此外，该组合显示出良好的鉴别早期HCC和失代偿性肝硬化的能力，AUC为0.81（95％CI 0.75-0.86）。
结论：

DCP可能是HCC早期诊断的补充生物标志物。构建的多标记预测算法可以有助于区分HCC与非恶性慢性肝病。
关键词：

早期发现;肝硬化;预测模型

结论：
    30022853
PMCID：
    PMC6044429
DOI：
    10.2147 / CMAR.S167036