Department of Hepato-Biliary-Pancreatic Surgery, The Affiliated Calmette Hospital of Kunming Medical University, The First People's Hospital of Kunming, Kunming, Yunnan, 650000, China.
Department of Clinical laboratory, Kunming Children's Hospital, Kunming, Yunnan, 650000, China.
BMC Gastroenterol. 2023 Jul 31;23(1):260. doi: 10.1186/s12876-023-02900-6.
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.
A training cohort was established including 103 HCC and 114 HC patients. 10 ml blood was collected from each patient with KEDTA 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.
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.
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.
甲基化 SEPT9（mSEPT9）似乎可有效用于肝细胞癌（HCC）检测。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 及其组合在肝硬化（HC）人群中的表现。
建立了一个训练队列，纳入了 103 例 HCC 和 114 例 HC 患者。每位患者均使用 KEDTA 管采集 10ml 血液，提取 3-4ml 血浆进行后续检测。通过训练队列优化 mSEPT9、AFP、PIVKA-II 及其组合的性能。使用包括 51 例 HCC 和 121 例 HC 患者的验证队列前瞻性验证检测性能。
在训练队列的最佳阈值下，mSEPT9、AFP 和 PIVKA-II 的灵敏度、特异性和曲线下面积（AUC）分别为 72.82%、89.47%、0.84，48.57%、89.92%、0.79，63.64%、95.95%、0.79。联合检测可将特异性为 86.84%时的灵敏度显著提高至 84.47%，AUC 为 0.91。所有单个标志物及其组合在血浆标志物水平、阳性检出率（PDR）和 AUC 中均观察到与分期相关的表现。mSEPT9 与 AFP 血浆水平之间存在中度相关性（r=0.527，P<0.0001）。三个标志物中的任意两个之间均具有良好的互补性，联合使用时可提供 HCC 检测的最佳灵敏度。随后的验证得出的 mSEPT9、AFP 和 PIVKA-II 的灵敏度、特异性和 AUC 分别为 65.31%、92.86%、0.80，44.24%、89.26%、0.75，62.22%、95.27%、0.78。联合检测可将特异性为 85.57%时的灵敏度显著提高至 84.00%，AUC 为 0.89。
与任何单个标志物相比，mSEPT9、AFP、PIVKA-II 的组合性能最佳，联合检测可能对 HC 人群中的 HCC 机会性筛查有效。
