Progress in research of serum markers for diagnosis of alpha-fetoprotein negative hepatocellular carcinoma

doi:10.3877/cma.j.issn.1674-0785.2024.07.010

Abstract

Abstract:

Hepatocellular carcinoma is currently the fourth most common malignant tumor and the second leading cause of cancer-related deaths in China， posing a serious threat to people's lives and health. Early diagnosis and treatment can significantly improve the survival rate and prognosis of liver cancer patients. The detection of serum biomarkers has significant clinical application value in early screening and diagnosis of liver cancer due to its simple operation. Alpha-fetoprotein is a highly specific serum biomarker for clinical diagnosis of hepatocellular carcinoma. However， in China， about 30%～40% of hepatocellular carcinoma patients test negative for alpha-fetoprotein， which greatly limits its role in the diagnosis of hepatocellular carcinoma. In recent years， the serum markers discovered by researchers， including protein markers， enzyme markers， cytokine markers， gene markers， and antigen/antibody markers， can compensate for the insufficiency of alpha-fetoprotein in hepatocellular carcinoma diagnosis. Therefore， the discovery and application of novel serum biomarkers has become an urgent need in clinical medicine in order to improve the early diagnosis rate of alpha-fetoprotein negative hepatocellular carcinoma.

Key words: Serum biomarkers, Alpha-fetoprotein negative, Hepatocellular carcinoma, Diagnosis

Ziyang Wang, Hongbin Wang, Xiaojing Liu. Progress in research of serum markers for diagnosis of alpha-fetoprotein negative hepatocellular carcinoma[J]. Chinese Journal of Clinicians(Electronic Edition), 2024, 18(07): 677-681.

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References 39

1	唐宇雁，谢仕斌，朱建芸. 甲胎蛋白和甲胎蛋白异质体比率（AFP-L3%）对HBV 相关早期肝细胞癌的诊断效能分析［J］. 临床肝胆病杂志， 2023， 39 （11）: 2607-2613.
2	Luo P， Wu S， Yu Y， et al. Current status and perspective biomarkers in AFP negative HCC: towards screening for and diagnosing hepatocellular carcinoma at an earlier stage ［J］. Pathol Oncol Res，2020， 26（2）: 599-603.
3	Zhang Z， Zhang Y， Wang Y， et al. Alpha-fetoprotein-L3 and Golgi protein 73 may serve as candidate biomarkers for diagnosing alphafetoprotein-negative hepatocellular carcinoma ［J］. Onco Targets Ther，2015， 9: 123-129.
4	丁华洋，王兴宇，刘学谦，等. GP73 和HSP90α 在低浓度甲胎蛋白原发性肝癌诊断中的应用价值［J］. 安徽医科大学学报， 2021， 56（8）: 1291-1294.
5	宋红亮，王建国，张会，等. 血清学标志物甲胎蛋白、PIVKA-Ⅱ和磷脂酰肌醇蛋白聚糖3 联合诊断肝癌的meta 分析［J］. 浙江大学学报（医学版）， 2024， 53 （1）: 131-139.
6	Liu S， Wang M， Zheng C， et al.Diagnostic value of serum glypican-3 alone and in combination with AFP as an aid in the diagnosis of liver cancer ［J］. Clin Biochem， 2020， 79: 54-60
7	Song Z， Chen W， Athavale D， et al. Osteopontin takes center stage in chronic liver disease ［J］. Hepatology.2021；73（4）: 1594-1608.
8	da Costa AN， Plymoth A， Santos-Silva D， et al. Osteopontin and latent-TGF β binding-protein 2 as potential diagnostic markers for HBVrelated hepatocellular carcinoma ［J］. Int J Cancer， 2015， 136（1）: 172-181.
9	Zhu M， Zheng J， Wu F， et al. OPN is a promising serological biomarker for hepatocellular carcinoma diagnosis ［J］. J Med Virol，2020， 92（12）: 3596-3603.
10	Wei W， Liu M， Ning S， et al. Diague of plasma HSP90α levels for detection of hepatocellular carcinoma ［J］. BMC Cancer， 2020， 20（1）: 6.
11	Luo P， Yin P， Hua R， et al. A Large-scale， multicenter serum metabolite biomarker identification study for the early detection of hepatocellular carcinoma ［J］. Hepatology， 2018， 67（2）: 662-675.
12	Fu Y， Xu X， Huang D， et al. Plasma heat shock protein 90alpha as a biomarker for the diagnosis of liver cancer: An official， large-scale，and multicenter clinical trial ［J］. EBioMedicine， 2017， 24: 56-63.
13	Zhou J， Yang W， Zhang S， et al. Diagnostic value of angiopoietin-like protein 2 for CHB-related hepatocellular carcinoma ［J］. Cancer Manag Res， 2019， 11: 7159-7169.
14	Kim DY， Toan BN， Tan CK， et al. Utility of combining PIVKA-II and AFP in the surveillance and monitoring of hepatocellular carcinoma in the Asia-Pacific region ［J］. Clin Mol Hepatol， 2023， 29（2）: 277-292.
15	Liu Z， Wu M， Lin D， et al. Des-gamma-carboxyprothrombin is a favorable biomarker for the early diagnosis of alfa-fetoproteinnegative hepatitis B virus-related hepatocellular carcinoma ［J］. J Int Med Res， 2020， 48（2）: 300060520902575.
16	段聪明. a-L-岩藻糖苷酶在原发性肝癌中的诊断价值［J］. 实用医技杂志， 2006， 13（24）: 4332-4334.
17	Shu H， Li W， Shang S， et al. Diagnosis of AFP-negative early-stage hepatocellular carcinoma using Fuc-PON1 ［J］. Discov Med， 2017，23（126）: 163-168.
18	Ye X， Li C， Zu X， et al. A large-scale multicenter study validates aldoketo reductase family 1 member B10 as a prevalent serum marker for detection of hepatocellular carcinoma ［J］. Hepatology， 2019， 69（6）:2489-2501.
19	Liu P， Lu D， Al-Ameri A， et al. Glutamine synthetase promotes tumor invasion in hepatocellular carcinoma through mediating epithelialmesenchymal transition ［J］. Hepatol Res， 2020， 50（2）: 246-257.
20	Song X， Wu A， Ding Z， et al. Soluble Axl is a novel diagnostic biomarker of hepatocellular carcinoma in Chinese patients with chronic hepatitis B virus Infection ［J］. Cancer Res Treat， 2020， 52（3）:789-797.
21	Lu Q， Li J， Cao H， et al. Comparison of diagnostic accuracy of Midkine and AFP for detecting hepatocellular carcinoma: a systematic review and meta-analysis ［J］. Biosci Rep， 2020， 40（3）: BSR20192424.
22	Zheng L， Li H， Huang J， et al. Serum midkine levels for the diagnosis and assessment of response to interventional therapy in patients with hepatocellular carcinoma ［J］. J Interv Med， 2020， 4（1）: 39-45.
23	Song BC， Chung YH， Kim JA， et al. Transforming growth factor-beta1 as a useful serologic marker of small hepatocellular carcinoma ［J］.Cancer， 2002， 94（1）: 175-180.
24	Gu Y， Li X， Bi Y， et al. CCL14 is a prognostic biomarker and correlates with immune infiltrates in hepatocellular carcinoma ［J］. Aging （Albany NY）， 2020， 12（1）: 784-807.
25	Sadeghi M， Lahdou I， Oweira H， et al. Serum levels of chemokines CCL4 and CCL5 in cirrhotic patients indicate the presence of hepatocellular carcinoma ［J］. Br J Cancer， 2015， 113（5）: 756-762.
26	Kong L， Zhou Y， Bu H， et al. Deletion of interleukin-6 in monocytes/macrophages suppresses the initiation of hepatocellular carcinoma in mice ［J］. J Exp Clin Cancer Res， 2016， 35（1）: 131.
27	Witjes CD， van Aalten SM， Steyerberg EW， et al. Recently introduced biomarkers for screening of hepatocellular carcinoma: a systematic review and meta-analysis ［J］. Hepatol Int， 2013， 7（1）: 59-64.
28	马文文，呼敏，王贵红，等. miR-103a-2、miR-122 和vaspin 在非酒精性脂肪性肝病合并HBV 感染中的表达及意义［J/OL］. 中华临床医师杂志（电子版）， 2022， 16（2）: 170-174.
29	Malik J， Klammer M， Rolny V， et al. Comprehensive evaluation of microRNA as a biomarker for the diagnosis of hepatocellular carcinoma ［J］. World J Gastroenterol， 2022， 28（29）: 3917-3933.
30	Tian Z， Yu T， Wei H， et al. Clinical value of LHPP-associated microRNAs combined with protein induced by vitamin K deficiency or antagonist-II in the diagnosis of alpha-fetoprotein-negative hepatocellular carcinoma ［J］. J Clin Lab Anal， 2020， 34（2）: e23071.
31	Zhou J， Yu L， Gao X， et al. Plasma microRNA panel to diagnose hepatitis B virus-related hepatocellular carcinoma ［J］. J Clin Oncol，2011， 29（36）: 4781-4788.
32	Yu J， Ding WB， Wang MC， et al. Plasma circular RNA panel to diagnose hepatitis B virus-related hepatocellular carcinoma: A largescale， multicenter study ［J］. Int J Cancer， 2020， 146（6）: 1754-1763.
33	侯志远，刘源，杨超然，等. 循环肿瘤DNA 在肝细胞癌中的研究现状及展望［J］. 临床肝胆病杂志， 2022， 38 （11）: 2616-2620.
34	Xiong Y， Xie CR， Zhang S， et al. Detection of a novel panel of somatic mutations in plasma cell-free DNA and its diagnostic value in hepatocellular carcinoma ［J］. Cancer Manag Res， 2019， 11: 5745-5756.
35	Zhu H. Squamous cell carcinoma antigen: clinical application and research status ［J］. Diagno stics （Basel）， 2022， 12（5）: 1065.
36	Giannelli G， Fransvea E， Trerotoli P， et al. Clinical validation of combined serological biomarkers for improved hepatocellular carcinoma diagnosis in 961 patients ［J］. Clin Chim Acta， 2007， 383（1-2）: 147-152.
37	Ezzikouri S， Kimura K， Sunagozaka H， et al. Serum DHCR24 autoantibody as a new biomarker for progression of hepatitis C ［J］.EBioMedicine， 2015， 2（6）: 604-612.
38	Yi CH， Weng HL， Zhou FG， et al. Elevated core-fucosylated IgG is a new marker for hepatitis B virus-related hepatocellular carcinoma ［J］.Oncoimmunology， 2015， 4（12）: e1011503.
39	Nomura F， Sogawa K， Noda K， et al. Serum anti-Ku86 is a potential biomarker for early detection of hepatitis C virus-related hepatocellular carcinoma ［J］. Biochem Biophys Res Commun， 2012， 21（4）: 837-843.

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