Cao Maomao, Shi Jufang, Xia Changfa, Li He, Cai Wei, Qi Xianyun, Dai Chunyun, Chen Wanqing
Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Department of Prevention and Control of Chronic Noncommunicable Diseases, Binhai County Center for Disease Control and Prevention, Binhai 224521, China.
Chin J Cancer Res. 2023 Feb 28;35(1):58-65. doi: 10.21147/j.issn.1000-9604.2023.01.06.
Circulating tumor DNA (ctDNA) and alpha-fetoprotein (AFP) plus ultrasound (US) have been considered to have high diagnostic accuracy for cancer detection, however, the efficacy of ctDNA methylation combined with the traditional detection modality of liver cancer has not been tested in a Chinese independent cohort.
The high-risk individuals aged between 35 and 70 years who were diagnosed with liver cirrhosis or had moderate and severe fatty liver were eligible for inclusion. All participants were invited to receive a traditional examination [referring to AFP plus US], and ctDNA methylation, respectively. The sensitivity and specificity of different diagnostic tools were calculated. The logistic regression model was applied to estimate the area under the curve (AUC), which was further validated by 10-fold internal cross-validation.
A total of 1,205 individuals were recruited in our study, and 39 participants were diagnosed with liver cancer. The sensitivity of AFP, US, US plus AFP, and the combination of US, AFP, and ctDNA methylation was 33.33%, 56.41%, 66.67%, and 87.18%, respectively. The corresponding specificity of AFP, US, US plus AFP, and the combination of all modalities was 98.20%, 99.31%, 97.68%, and 97.68%, respectively. The AUCs of AFP, US, US plus AFP, and the combination of AFP, US, and ctDNA methylation were 65.77%, 77.86%, 82.18%, and 92.43%, respectively. The internally validated AUCs of AFP, US, US plus AFP, and the combination of AFP, US, and ctDNA methylation were 67.57%, 83.26%, 86.54%, and 93.35%, respectively.
The ctDNA methylation is a good complementary to AFP and US for the detection of liver cancer.
循环肿瘤DNA（ctDNA）以及甲胎蛋白（AFP）联合超声（US）被认为在癌症检测中具有较高的诊断准确性，然而，ctDNA甲基化联合肝癌传统检测方式的有效性尚未在中国独立队列中得到验证。
纳入年龄在35至70岁之间、被诊断为肝硬化或患有中度和重度脂肪肝的高危个体。所有参与者分别接受传统检查[即AFP联合US]以及ctDNA甲基化检测。计算不同诊断工具的敏感性和特异性。应用逻辑回归模型估计曲线下面积（AUC），并通过10倍内部交叉验证进一步验证。
本研究共招募了1205名个体，其中39名参与者被诊断为肝癌。AFP、US、US联合AFP以及US、AFP与ctDNA甲基化联合检测的敏感性分别为33.33%、56.41%、66.67%和87.18%。AFP、US、US联合AFP以及所有检测方式联合的相应特异性分别为98.20%、99.31%、97.68%和97.68%。AFP、US、US联合AFP以及AFP、US与ctDNA甲基化联合检测的AUC分别为65.77%、77.86%、82.18%和92.43%。AFP、US、US联合AFP以及AFP、US与ctDNA甲基化联合检测的内部验证AUC分别为67.57%、83.26%、86.54%和93.35%。
ctDNA甲基化在肝癌检测中是AFP和US的良好补充。
