血清膜联蛋白 A3 在肝细胞癌患者的诊断、预后预测和治疗反应评估中的应用。
Application of Serum Annexin A3 in Diagnosis, Outcome Prediction and Therapeutic Response Evaluation for Patients with Hepatocellular Carcinoma.
机构信息
Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Blood Transfusion, Zhongshan Hospital, Shanghai, China.
出版信息
Ann Surg Oncol. 2018 Jun;25(6):1686-1694. doi: 10.1245/s10434-018-6402-0. Epub 2018 Apr 6.
PURPOSE
Annexin A3 (ANXA3) could induce progression of hepatocellular carcinoma (HCC) via promoting stem cell traits of CD133-positive cells. Moreover, serum ANXA3 showed preliminary diagnostic potential, however further validation was required. Meanwhile, the prognostic value of ANXA3 remained elusive. The present study aimed to validate diagnostic performance and further systematically investigate the prognostic value of serum ANXA3.
METHODS
Serum ANXA3 of 368 HCC patients was determined by enzyme-linked immunosorbent assay (ELISA); 295 of these patients underwent resection and 73 underwent transcatheter arterial chemoembolization (TACE). Diagnostic performance of ANXA3 was evaluated by receiver operating characteristic (ROC) analysis, and the prognostic value was evaluated by Cox regression and Kaplan-Meier analysis. To evaluate the relationship between serum ANXA3 and circulating CD133 mRNA-positive tumor cells (CD133 CTCs), real-time polymerase chain reaction was conducted in 69 patients who underwent resection.
RESULTS
Serum ANXA3 provided greater diagnostic performance than α-fetoprotein (area under the curve [AUC] 0.869 vs. 0.782), especially in early diagnosis (AUC 0.852 vs. 0.757) and discriminating HCC from patients at risk (0.832 vs. 0.736). Pretreatment ANXA3 was an independent predictor of tumor recurrence (hazard ratio [HR] 1.87, 95% confidence interval [CI] 1.26-2.76, p = 0.002)/progression (HR 1.88, 95% CI 1.04-3.43, p = 0.038) and survival (resectable: HR 2.26, 95% CI 1.44-3.56, p = 0.001; unresectable: HR 2.08, 95% CI 1.10-4.05, p = 0.025), and retained its performance in low-recurrence-risk subgroups. Specifically, dynamic changes of ANXA3-positive status was associated with worse prognosis. ANXA3 was positively correlated with CD133 CTCs (r = 0.601, p < 0.001). In patients with detectable CD133 CTC, high ANXA3 was positively associated with a higher risk of recurrence and shorter overall survival.
CONCLUSIONS
Serum ANXA3 shows promise as a biomarker for diagnosis, outcome prediction, and therapeutic response evaluation in patients with HCC.
目的
膜联蛋白 A3（ANXA3）可通过促进 CD133 阳性细胞的干细胞特性来诱导肝细胞癌（HCC）的进展。此外，血清 ANXA3 具有初步的诊断潜力，但需要进一步验证。同时，ANXA3 的预后价值仍不清楚。本研究旨在验证诊断性能，并进一步系统地研究血清 ANXA3 的预后价值。
方法
采用酶联免疫吸附试验（ELISA）检测 368 例 HCC 患者的血清 ANXA3；其中 295 例患者接受了肝切除术，73 例患者接受了经导管动脉化疗栓塞术（TACE）。通过接受者操作特征（ROC）分析评估 ANXA3 的诊断性能，并通过 Cox 回归和 Kaplan-Meier 分析评估预后价值。为了评估血清 ANXA3 与循环 CD133 mRNA 阳性肿瘤细胞（CD133 CTCs）之间的关系，对 69 例接受肝切除术的患者进行了实时聚合酶链反应。
结果
血清 ANXA3 提供了比甲胎蛋白（AFP）更好的诊断性能（曲线下面积[AUC] 0.869 比 0.782），尤其是在早期诊断（AUC 0.852 比 0.757）和区分 HCC 与高危患者（AUC 0.832 比 0.736）方面。术前 ANXA3 是肿瘤复发（危险比[HR] 1.87，95%置信区间[CI] 1.26-2.76，p=0.002）/进展（HR 1.88，95% CI 1.04-3.43，p=0.038）和生存（可切除：HR 2.26，95% CI 1.44-3.56，p=0.001；不可切除：HR 2.08，95% CI 1.10-4.05，p=0.025）的独立预测因子，并且在低复发风险亚组中仍保持其性能。具体而言，ANXA3 阳性状态的动态变化与预后不良相关。ANXA3 与 CD133 CTCs 呈正相关（r=0.601，p<0.001）。在可检测到 CD133 CTC 的患者中，高 ANXA3 与更高的复发风险和更短的总生存期相关。
结论
血清 ANXA3 有望成为 HCC 患者诊断、预后预测和治疗反应评估的生物标志物。
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