背景:甲基化SEPT9(mSEPT9)似乎对肝细胞癌(HCC)检测有效。然而,其在高危人群中的表现尚未得到验证。我们设计了一项初步研究,旨在调查mSEPT9,AFP,PIVKA-II及其在肝硬化(HC)人群中的组合。
方法:建立了一个包括103例HCC和114例HC患者的训练队列。用K2EDTA管收集每位患者的10ml血液,并提取3-4ml血浆用于后续测试。mSEPT9,AFP,PIVKA-II及其组合通过训练队列进行了优化。测试性能通过验证队列进行了前瞻性验证,包括51例HCC和121例HC患者。
结果:在训练队列中的最佳阈值下,灵敏度,特异性和曲线下面积(AUC)为72.82%,89.47%,0.84和48.57%,89.92%,0.79,63.64%,95.95%,mSEPT9、AFP和PIVKA-II为0.79,分别。联合检测在86.84%的特异性和0.91的AUC下,灵敏度显着提高到84.47%(P<0.05)。在血浆标志物水平中观察到所有单一标志物及其组合的阶段依赖性表现,阳性检出率(PDR)和AUC。mSEPT9与AFP血浆水平呈中等相关性(r=0.527,P<0.0001)。在三个标记中的任何两个之间发现了良好的互补性,结合使用时,在HCC检测中提供最佳灵敏度。随后的验证达到了灵敏度,特异性和AUC为65.31%,92.86%,0.80和44.24%,89.26%,0.75和62.22%,95.27%,mSEPT9、AFP和PIVKA-II为0.78,分别。联合检测在85.57%的特异性上产生84.00%(P<0.05)的灵敏度显着增加,AUC为0.89。
结论:mSEPT9、AFP、PIVKA-II与任何单一标记相比,并且该组合可能对HC人群中的HCC机会性筛查有效。
BACKGROUND: The methylation SEPT9 (mSEPT9) appeared to be effective for hepatocellular carcinoma (HCC) detection. However, its performance in high-risk population has not been validated. We designed a pilot study and aimed to investigate the performance of mSEPT9, AFP, PIVKA-II and their combination in hepatic cirrhosis (HC) population.
METHODS: A training cohort was established including 103 HCC and 114 HC patients. 10 ml blood was collected from each patient with K2EDTA tubes, and 3-4 ml plasma was extracted for subsequent tests. The performance of mSEPT9, AFP, PIVKA-II and their combination was optimized by the training cohort. Test performance was prospectively validated with a validation cohort, including 51 HCC and 121 HC patients.
RESULTS: At the optimal thresholds in the training cohort, the sensitivity, specificity and area under curve (AUC) was 72.82%, 89.47%, 0.84, and 48.57%, 89.92%, 0.79, and 63.64%, 95.95%, 0.79 for mSEPT9, AFP and PIVKA-II, respectively. The combined test significantly increased the sensitivity to 84.47% (P < 0.05) at the specificity of 86.84% with an AUC of 0.91. Stage-dependent performance was observed with all single markers and their combination in plasma marker levels, positive detection rate (PDR) and AUC. Moderate correlation was found between mSEPT9 and AFP plasma levels (r = 0.527, P < 0.0001). Good complementarity was found between any two of the three markers, providing optimal sensitivity in HCC detection when used in combination. Subsequent validation achieved a sensitivity, specificity and AUC of 65.31%, 92.86%, 0.80, and 44.24%, 89.26%, 0.75, and 62.22%, 95.27%, 0.78 for mSEPT9, AFP and PIVKA-II, respectively. The combined test yielded a significantly increased sensitivity of 84.00% (P < 0.05) at 85.57% specificity, with an AUC at 0.89.
CONCLUSIONS: The performance was optimal by the combination of mSEPT9, AFP, PIVKA-II compared with any single marker, and the combination may be effective for HCC opportunistic screening in HC population.