血清肿瘤标志物在肝细胞癌早期诊断中的应用

doi:10.3969/j.issn.1004-583X.2024.06.014

摘要/Abstract

摘要：

肝细胞癌(hepatocellular carcinoma,HCC)是目前世界上最常见的恶性肿瘤之一,早期无明显症状,常隐匿起病,但发展和转移极为迅速。多数肝癌诊断时已属晚期,病死率高。要达到早期诊疗效果,选择经济有效的诊断方法尤为重要。血清肿瘤标志物具有无创性、可重复分析、实时监测的特点,其在HCC早期诊断中具有重要的应用价值。近几年,HCC肿瘤标志物研究发展迅速,甲胎蛋白是临床上最常用的生物标志物,但其诊断效能并不理想。其他肿瘤标志物如甲胎蛋白异质体、异常凝血酶原、高尔基体蛋白-73、骨桥蛋白、磷脂酰肌醇蛋白聚糖3、微小核糖核酸、肝素结合细胞因子等也进行了许多临床应用研究。联合这些生物标志物建立预测模型可提高HCC早期诊断效能,也是其治疗和疗效评价的潜在靶点。

关键词: 肝肿瘤, 血清肿瘤标志物, 早期诊断, 预测模型

中图分类号:

R735.7

申彤彤, 匡竞, 王玮. 血清肿瘤标志物在肝细胞癌早期诊断中的应用[J]. 临床荟萃, 2024, 39(6): 563-567.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2024.06.014

https://huicui.hebmu.edu.cn/CN/Y2024/V39/I6/563

参考文献 43

[1]	Wei W, Zeng H, Zheng R, et al. Cancer registration in China and its role in cancer prevention and control[J]. Lancet Oncol, 2020, 21(7): e342-e349.
[2]	Shahini E, Pasculli G, Solimando AG, et al. Updating the clinical application of blood biomarkers and their algorithms in the diagnosis and surveillance of hepatocellular carcinoma: A critical review[J]. Int J Mol Sci, 2023, 24(5):4286.
[3]	Foerster F, Galle PR. Comparison of the current international guidelines on the management of HCC[J]. JHEP Rep, 2019, 1(2): 114-119. doi: 10.1016/j.jhepr.2019.04.005 pmid: 32039359
[4]	Tatarinov YS, Afanaseva AV, Parfenova LF. Formation of serum proteins in human ontogeny[J]. Fed Proc Transl Suppl, 1964, 23: 437-440. pmid: 14185871
[5]	Zong J, Fan Z, Zhang Y. Serum tumor markers for early diagnosis of primary hepatocellular carcinoma[J]. J Hepatocell Carcinoma, 2020, 7: 413-422. doi: 10.2147/JHC.S272762 pmid: 33376710
[6]	Sauzay C, Petit A, Bourgeois AM, et al. Alpha-foetoprotein (AFP): A multi-purpose marker in hepatocellular carcinoma[J]. Clin Chim Acta, 2016, 463: 39-44. doi: S0009-8981(16)30403-X pmid: 27732875
[7]	Carr BI, Akkiz H, Üsküdar O, et al. HCC with low- and normal-serum alpha-fetoprotein levels[J]. Clin Pract (Lond), 2018, 15(1): 453-464.
[8]	Chan SL, Mo F, Johnson PJ, et al. Performance of serum α-fetoprotein levels in the diagnosis of hepatocellular carcinoma in patients with a hepatic mass[J]. HPB (Oxford), 2014, 16(4): 366-372.
[9]	Pinero F, Dirchwolf M, Pessoa MG. Biomarkers in hepatocellular carcinoma: Diagnosis, prognosis and treatment response assessment[J]. Cells, 2020, 9(6):1370.
[10]	Zhang Z, Zhang Y, Wang Y, et al. Alpha-fetoprotein-L3 and Golgi protein 73 may serve as candidate biomarkers for diagnosing alpha-fetoprotein-negative hepatocellular carcinoma[J]. Onco Targets Ther, 2016, 9: 123-129.
[11]	Marrero JA, Feng Z, Wang Y, et al. Alpha-fetoprotein, des-gamma carboxyprothrombin, and lectin-bound alpha-fetoprotein in early hepatocellular carcinoma[J]. Gastroenterology, 2009, 137(1): 110-118. doi: 10.1053/j.gastro.2009.04.005 pmid: 19362088
[12]	Choi JY, Jung SW, Kim HY, et al. Diagnostic value of AFP-L3 and PIVKA-II in hepatocellular carcinoma according to total-AFP[J]. World J Gastroenterol, 2013, 19(3): 339-346.
[13]	Choi J, Kim GA, Han S, et al. Longitudinal assessment of three serum biomarkers to detect very early-stage hepatocellular carcinoma[J]. Hepatology, 2019, 69(5): 1983-1994. doi: 10.1002/hep.30233 pmid: 30153338
[14]	Zhang JW, Guan LY, E CY, et al. The value of serum abnormal prothrombin in clinical application of hepatocellular carcinoma[J]. Zhonghua Wai Ke Za Zhi, 2020, 58(10): 776-781.
[15]	Feng H, Li B, Li Z, et al. PIVKA-II serves as a potential biomarker that complements AFP for the diagnosis of hepatocellular carcinoma[J]. BMC Cancer, 2021, 21(1): 401.
[16]	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.
[17]	Ng WY, Lim DYZ, Tan SY, et al. The role of PIVKA-II in hepatocellular carcinoma surveillance in an Asian population[J]. Ann Acad Med Singap, 2023, 52(2): 108-110. doi: 10.47102/annals-acadmedsg.2022351 pmid: 36880824
[18]	Liu Z, Wu M, Lin D, et al. Des-gamma-carboxyprothrombin is a favorable biomarker for the early diagnosis of alfa-fetoprotein-negative hepatitis B virus-related hepatocellular carcinoma[J]. J Int Med Res, 2020, 48(2): 300060520902575.
[19]	Li T, Li H, Wang A, et al. Development and validation of a simple model for detection of early hepatocellular carcinoma in a liver cirrhosis cohort[J]. Cancer Manag Res, 2019, 11: 9379-9386. doi: 10.2147/CMAR.S221050 pmid: 31807067
[20]	Liang R, Liu Z, Piao X, et al. Research progress on GP73 in malignant tumors[J]. Onco Targets Ther, 2018, 11: 7417-7421.
[21]	Wei H, Li B, Zhang R, et al. Serum GP73, a marker for evaluating progression in patients with chronic HBV infections[J]. PLoS One, 2013, 8(2): e53862.
[22]	Ar NZ, El Kassas M, Salam ESE, et al. The possible role of Dickkopf-1, Golgi protein- 73 and midkine as predictors of hepatocarcinogenesis: A review and an Egyptian study[J]. Sci Rep, 2020, 10(1): 5156.
[23]	Han X, Wang W, He J, et al. Osteopontin as a biomarker for osteosarcoma therapy and prognosis[J]. Oncol Lett, 2019, 17(3): 2592-2598. doi: 10.3892/ol.2019.9905 pmid: 30854034
[24]	Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American association for the study of liver diseases[J]. Hepatology, 2018, 68(2): 723-750. doi: 10.1002/hep.29913 pmid: 29624699
[25]	Zhao S, Long M, Zhang X, et al. The diagnostic value of the combination of Golgi protein 73, glypican-3 and alpha-fetoprotein in hepatocellular carcinoma: A diagnostic meta-analysis[J]. Ann Transl Med, 2020, 8(8): 536.
[26]	Jiang D, Zhang Y, Wang Y, et al. Diagnostic accuracy and prognostic significance of Glypican-3 in hepatocellular carcinoma: A systematic review and meta-analysis[J]. Front Oncol, 2022, 12: 1012418.
[27]	Ibrahim TR, Abdel-Raouf SM. Immunohistochemical study of Glypican-3 and HepPar-1 in differentiating hepatocellular carcinoma from metastatic carcinomas in FNA of the liver[J]. Pathol Oncol Res, 2015, 21(2): 379-387. doi: 10.1007/s12253-014-9830-6 pmid: 25108409
[28]	Caviglia GP, Ciruolo M, Abate ML, et al. Alpha-fetoprotein, protein induced by vitamin K absence or antagonist II and Glypican-3 for the detection and prediction of hepatocellular carcinoma in patients with cirrhosis of viral etiology[J]. Cancers (Basel), 2020, 12(11):3218.
[29]	Wang JY, Wang XK, Zhu GZ, et al. Distinct diagnostic and prognostic values of glypicans gene expression in patients with hepatocellular carcinoma[J]. BMC Cancer, 2021, 21(1): 462.
[30]	Zhou Y, Ren H, Dai B, et al. Hepatocellular carcinoma-derived exosomal miRNA-21 contributes to tumor progression by converting hepatocyte stellate cells to cancer-associated fibroblasts[J]. J Exp Clin Cancer Res, 2018, 37(1): 324.
[31]	Yin H, Peng X, Ren P, et al. MicroRNAs as a novel class of diagnostic biomarkers in detection of hepatocellular carcinoma: A meta-analysis[J]. Tumour Biol, 2014, 35(12): 12317-12326.
[32]	Zhang T, Yang Z, Kusumanchi P, et al. Critical role of microRNA-21 in the pathogenesis of liver diseases[J]. Front Med (Lausanne), 2020, 7: 7.
[33]	Oura K, Morishita A, Masaki T. Molecular and functional roles of microRNAs in the progression of hepatocellular carcinoma-a review[J]. Int J Mol Sci, 2020, 21(21):8362.
[34]	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.
[35]	Gowhari Shabgah A, Ezzatifar F, Aravindhan S, et al. Shedding more light on the role of midkine in hepatocellular carcinoma: New perspectives on diagnosis and therapy[J]. IUBMB Life, 2021, 73(4): 659-669. doi: 10.1002/iub.2458 pmid: 33625758
[36]	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.
[37]	Singal AG, Tayob N, Mehta A, et al. GALAD demonstrates high sensitivity for HCC surveillance in a cohort of patients with cirrhosis[J]. Hepatology, 2022, 75(3): 541-549.
[38]	Berhane S, Toyoda H, Tada T, et al. Role of the GALAD and BALAD-2 serologic models in diagnosis of hepatocellular carcinoma and prediction of survival in patients[J]. Clin Gastroenterol Hepatol, 2016, 14(6): 875-886.e6.
[39]	Li L, Lu F, Chen P, et al. Validation of the GALAD model and establishment of a new model for HCC detection in Chinese patients[J]. Front Oncol, 2022, 12: 1037742.
[40]	Xu RH, Wei W, Krawczyk M, et al. Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma[J]. Nat Mater, 2017, 16(11): 1155-1161.
[41]	Lin XJ, Chong Y, Guo ZW, et al. A serum microRNA classifier for early detection of hepatocellular carcinoma: A multicentre, retrospective, longitudinal biomarker identification study with a nested case-control study[J]. Lancet Oncol, 2015, 16(7): 804-815.
[42]	Yang T, Xing H, Wang G, et al. A novel online calculator based on serum biomarkers to detect hepatocellular carcinoma among patients with hepatitis B[J]. Clin Chem, 2019, 65(12): 1543-1553. doi: 10.1373/clinchem.2019.308965 pmid: 31672853
[43]	Toyoda H, Tada T, Johnson PJ, et al. Validation of serological models for staging and prognostication of HCC in patients from a Japanese nationwide survey[J]. J Gastroenterol, 2017, 52(10): 1112-1121. doi: 10.1007/s00535-017-1321-6 pmid: 28224228

血清肿瘤标志物在肝细胞癌早期诊断中的应用

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献 43

相关文章 15

编辑推荐

Metrics

本文评价

[1]	赵旭辉, 黄小敏, 达德转, 许焱, 崔晓东, 李红玲. 基于生物信息学筛选影响胃癌患者预后的糖酵解相关基因[J]. 临床荟萃, 2024, 39(1): 20-29.
[2]	李亚, 杜涛明, 邱世香, 陈超, 钟立明. 伴有抑郁症状肝癌患者脑功能连接研究[J]. 临床荟萃, 2023, 38(6): 532-536.
[3]	李亚, 邱世香, 陈超, 钟立明. 肝癌患者抑郁相关因素及其与生活质量的关系[J]. 临床荟萃, 2022, 37(6): 539-543.
[4]	郭小军, 孔延亮, 刘涛, 成正祥, 张睿, 樊雷. CT引导经皮射频消融术治疗肝癌分析[J]. 临床荟萃, 2021, 36(9): 807-810.
[5]	谢志海, 周志聪, 桂元, 孙静锋. IGF1R反义非编码RNA在肝癌中的差异化表达[J]. 临床荟萃, 2021, 36(7): 620-622.
[6]	陈佳a，徐华b. 血清蛋白电泳(α2+β)/Alb比值联合胱抑素C在糖尿病肾脏疾病早期诊断中的临床价值[J]. 临床荟萃, 2019, 34(9): 814-818.
[7]	齐雪姣a，卜晖a，邹月丽a，杨建凯b，赵银龙b，何俊瑛a. 难治性真菌性脑膜炎3例并文献复习[J]. 临床荟萃, 2019, 34(2): 154-157.
[8]	孙婷婷1，郭健2a，孙雯雯2b，赵燕珍1，刘丽敏1，朱斌1. 慢性丙型肝炎患者合并糖尿病对肝癌发生率影响的Meta分析[J]. 临床荟萃, 2018, 33(6): 519-524,531.
[9]	李媛1,2, 王鑫1, 赵彩彦1，. 终末期肝病继发感染的危险因素评估与早期诊断[J]. 临床荟萃, 2018, 33(12): 1091-1095,1101.
[10]	黄洁1，2，聂芳1，杨理雯2，李静1. 超声评价2型糖尿病患者并发原发性肝癌特点及相关因素分析[J]. 临床荟萃, 2017, 32(10): 873-876.
[11]	刘慧敏, 刘平. 采用ROC曲线评价a-L-岩藻糖苷酶,5-核苷酸酶,甲胎蛋白在肝癌诊断、预后预测中的价值[J]. 临床荟萃, 2016, 31(4): 414-417.
[12]	金发光. 支气管镜新技术在肺癌早期诊断中的应用[J]. 临床荟萃, 2016, 31(11): 1161-1166.
[13]	赵宝宏，徐倩，曾艳红，郭志军，蔺强，张玉环. 钆喷酸葡胺对肝实质及肝内常见恶性病变T2加权成像的影响[J]. 临床荟萃, 2016, 31(11): 1244-1247.
[14]	郑建晓;吴金明. 扶正补虚方对原发性肝癌患者T细胞亚群及血管生成相关因子影响[J]. 临床荟萃, 2015, 30(9): 1036-1038.
[15]	黄伟;李芹;官升灿;刘路;周文. 组合检测指标在手足口病早期诊断中的价值[J]. 临床荟萃, 2015, 30(7): 785-788.