HBV相关肝细胞癌患者血清ADAMTS13、GDF-15、ANGPTL6水平及其与肝癌的相关性

肝脏 ›› 2026, Vol. 31 ›› Issue (2): 211-214.

HBV相关肝细胞癌患者血清ADAMTS13、GDF-15、ANGPTL6水平及其与肝癌的相关性

赵伟, 马敏, 许巧云, 张健

211200 南京南京市溧水区人民医院检验科(赵伟,许巧云,张健);211300 南京南京市高淳人民医院检验科(马敏)

收稿日期:2025-01-30 出版日期:2026-02-28 发布日期:2026-04-17
通讯作者: 张健,Email:zj791405805@126.com
基金资助:
南京市卫生科技发展专项基金项目(YKK21126)

Serum levels of ADAMTS13, GDF-15, and ANGPTL6 in patients with HBV-related hepatocellular carcinoma and their correlation with hepatocellular carcinoma

ZHAO Wei¹, MA Min², XU Qiao-yun¹, ZHANG Jian¹

1. Department of Laboratory Medicine, Lishui District People's Hospital, Nanjing 211200, China;
2. Department of Laboratory Medicine, Nanjing Gaochun People's Hospital, Nanjing 211300, China

Received:2025-01-30 Online:2026-02-28 Published:2026-04-17
Contact: ZHANG Jian,Email:zj791405805@126.com

摘要/Abstract

摘要： 目的探究HBV相关肝细胞癌患者血清人金属肽酶含血小板反应蛋白13(ADAMTS13)、生长分化因子-15(GDF-15)和血管生成素样蛋白6(ANGPTL6)水平及其与肝癌的相关性。方法选取2020年6月至2023年12月南京市溧水区人民医院和南京市高淳人民医院收治的HBV相关肝细胞癌患者80例,选取同期慢性HBV感染者80例。比较两组患者一般资料和血清ADAMTS13、GDF-15和ANGPTL6水平。采用多元logistic分析HBV相关肝癌的危险因素,以受试者工作特征曲线下面积(AUROC)评估各因素对肝癌发生的诊断价值。结果肝癌组血清ADAMTS13、GDF-15和ANGPTL6水平分别为(975.15±191.60)ng/mL、(1.61±0.29)ng/mL、(163.66±47.40)ng/mL,均低于HBV组的(1 140.63±158.34)ng/mL、(2.03±0.43)ng/mL、(199.58±44.86)ng/mL。Logistic回归分析结果显示,低ADAMTS13、GDF-15和ANGPTL6水平和高HBV DNA水平均为HBV相关肝细胞癌发生的独立危险因素(P<0.05)。ADAMTS13、GDF-15和ANGPTL6对HBV慢性感染者肝癌发生的预测灵敏度分别为52.5%、73.8%和65.0%,特异度分别为88.7%、71.3%和71.3%,AUC分别为0.745、0.787和0.711。当ADAMTS13、GDF-15和ANGPTL6联合预测时,灵敏度和特异度分别为70.0%和88.7%,AUC为0.878。结论 HBV相关肝细胞癌患者血清中ADAMTS13、GDF-15和ANGPTL6水平显著降低,且这些标志物的表达水平与肝癌发生密切相关,动态监测以上指标可能有助于肝癌的早期预警和预后判断。

关键词: 乙型肝炎病毒, 肝细胞癌, 人金属肽酶含血小板反应蛋白13, 生长分化因子-15, 血管生成素样蛋白6

Abstract: Objective To investigate the serum levels of a disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13), growth differentiation factor-15 (GDF-15), and angiopoietin-like protein 6 (ANGPTL6) in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) and their correlation with HCC. Methods Eighty patients with HBV-related HCC admitted to Nanjing Lishui People's Hospital and Nanjing Gaochun People's Hospital between June 2020 and December 2023 were selected as the observation group, and 80 patients with chronic HBV infection during the same period were selected as the control group. General data, and serum levels of ADAMTS13, GDF-15, and ANGPTL6 of the two groups were compared. Multivariate logistic analysis was used to identify the risk factors associated with the HBV-related HCC, and the diagnostic value of each factor in predicting HCC occurrence was assessed by receiver operating characteristic (ROC) curves. Results The serum levels of ADAMTS13, GDF-15, and ANGPTL6 in the observation group were (975.15±191.60) ng/mL, (1.61±0.29) ng/mL, and (163.66±47.40) ng/mL, respectively, lower than those in the control group [(1 140.63±158.34) ng/mL, (2.03±0.43) ng/mL, and (199.58±44.86) ng/mL]. Logistic regression analysis showed that low levels of ADAMTS13, GDF-15, and ANGPTL6, and high levels of HBV DNA, were independent risk factors for the occurrence of HBV-related HCC (P<0.05). ROC curve analysis indicated that the sensitivity of ADAMTS13, GDF-15, and ANGPTL6 in predicting HCC occurrence in chronic HBV-infected patients was 52.5%, 73.8%, and 65.0%, respectively. The specificity was 88.7%, 71.3%, and 71.3%, respectively, with are under the curve (AUC) of 0.745, 0.787, and 0.711. When ADAMTS13, GDF-15, and ANGPTL6 were combined for prediction, the sensitivity and specificity increased to 70.0% and 88.7%, respectively, with an AUC of 0.878. Conclusion Serum levels of ADAMTS13, GDF-15, and ANGPTL6 are significantly reduced in patients with HBV-related HCC, and the expression levels of these biomarkers are closely related to the occurrence of HCC. Dynamic monitoring of these markers may contribute to the early warning and prognosis of HCC.

Key words: Hepatitis B virus, Hepatocellular carcinoma, A disintegrin and metalloproteinase with thrombospondin motifs 13, Growth differentiation factor-15, Angiopoietin-like protein 6

赵伟, 马敏, 许巧云, 张健. HBV相关肝细胞癌患者血清ADAMTS13、GDF-15、ANGPTL6水平及其与肝癌的相关性[J]. 肝脏, 2026, 31(2): 211-214.

ZHAO Wei, MA Min, XU Qiao-yun, ZHANG Jian. Serum levels of ADAMTS13, GDF-15, and ANGPTL6 in patients with HBV-related hepatocellular carcinoma and their correlation with hepatocellular carcinoma[J]. Chinese Hepatolgy, 2026, 31(2): 211-214.

/ 推荐

参考文献

[1] 金超,李小婷,刘宏宇,等. HBV DNA整合诱发肝细胞癌分子机制的研究进展[J]. 肝脏,2024,29(6):731-735.
[2] 卢君瑶,王登宇,尹东林,等. HBV相关肝细胞癌的临床特征及危险因素分析[J]. 肝脏,2020,25(3):285-287.
[3] 牛义善,曾强. 炎症生物标志物对肝癌肝移植预后的预测作用[J]. 器官移植,2022,13(1):49-54.
[4] Théret N, Bouezzeddine F, Azar F, et al. ADAM and ADAMTS proteins, new players in the regulation of hepatocellular carcinoma microenvironment[J]. Cancers, 2021, 13(7): 1563.
[5] 高云鸽,程天一,钱罗蒙,等. GDF-15在肿瘤发生发展及免疫调节中作用的研究进展[J]. 中国免疫学杂志,2020,36(14):1784-1787.
[6] 胡伟婷,李兴. 血管生成素样蛋白6与肥胖及其相关疾病的研究进展[J]. 国际内分泌代谢杂志,2021,41(3):229-232.
[7] 中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗指南(2022年版)[J]. 中华消化外科杂志,2022,21(2):143-168.
[8] Zheng Q I, Zou B, Wu Y, et al. Systematic review with meta‐analysis: prevalence of hepatic steatosis, fibrosis and associated factors in chronic hepatitis B[J]. Aliment Pharm Ther, 2021, 54(9): 1100-1109.
[9] Rizzo G E M, Cabibbo G, Craxì A. Hepatitis B virus-associated hepatocellular carcinoma[J]. Viruses, 2022, 14(5): 986.
[10] Johnson P, Zhou Q, Dao D Y, et al. Circulating biomarkers in the diagnosis and management of hepatocellular carcinoma[J]. Nat Rev Gastro Hepat, 2022, 19(10): 670-681.
[11] Debes J D, Romagnoli P A, Prieto J, et al. Serum biomarkers for the prediction of hepatocellular carcinoma[J]. Cancers, 2021, 13(7): 1681.
[12] Parikh N D, Mehta A S, Singal A G, et al. Biomarkers for the early detection of hepatocellular carcinoma[J]. Cancer Epidem Biomar, 2020, 29(12): 2495-2503.
[13] Takaya H, Namisaki T, Kitade M, et al. VWF/ADAMTS13 ratio as a potential biomarker for early detection of hepatocellular carcinoma[J]. BMC Gastroenterol, 2019, 19(1): 1-10.
[14] Galuppo B, Agazzi C, Pierpont B, et al. Growth differentiation factor 15 (GDF15) is associated with non-alcoholic fatty liver disease (NAFLD) in youth with overweight or obesity[J]. Nutr Diabetes, 2022, 12(1): 9.
[15] Zuo D, Xiao J, An H, et al. Screening for lipid-metabolism-related genes and identifying the diagnostic potential of ANGPTL6 for HBV-related early-stage hepatocellular carcinoma[J]. Biomolecules, 2022, 12(11): 1700.
[16] Bai Y, Lu D, Qu D, et al. The role of ANGPTL gene family members in hepatocellular carcinoma[J]. Dis Markers, 2022, 2022(1): 1844352.