ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 39 Issue 10
Oct.  2023
Turn off MathJax
Article Contents

Research advances in the role of blood metabolic markers in the treatment response and prognosis prediction of primary liver cancer

DOI: 10.3969/j.issn.1001-5256.2023.10.028
Research funding:

Natural Science Foundation of Chongqing (2022NSCQ-MSX1038);

Natural Science Foundation of Chongqing (2022NSCQ-MSX0775)

More Information
  • Corresponding author: HE Song, hedoctor65@cqmu.edu.cn (ORCID: 0000-0002-6424-4974)
  • Received Date: 2022-12-27
  • Accepted Date: 2023-02-21
  • Published Date: 2023-10-30
  • Primary liver cancer is one of the most severe cancer burdens around the world. Metabolic reprogramming is one phenotype of cancer, and blood metabolic markers are closely associated with metabolic reprogramming and can predict the risk of recurrence and survival or assess the treatment response of liver cancer, with important significance in the stratified management of patients, the development of rational treatment strategies, and the improvement of patient prognosis. By reviewing the recent studies on blood metabolomics in assessing the treatment response or predicting the prognosis of liver cancer, this article summarizes the blood metabolites with predictive significance and their mechanism of action and analyzes the current research status, existing problems, and prospects of this field. It is believed that the metabolites, such as aromatic amino acids, lipids, and bile acids, have an important clinical value in predicting the prognosis of liver cancer, and metabolomics technology has great potential in finding useful metabolites, but there are still many issues to be solved, such as technical limitations, insufficient studies, and multiple influencing factors.


  • loading
  • [1]
    RUMGAY H, ARNOLD M, FERLAY J, et al. Global burden of primary liver cancer in 2020 and predictions to 2040[J]. J Hepatol, 2022, 77( 6): 1598- 1606. DOI: 10.1016/j.jhep.2022.08.021.
    XIA C, DONG X, LI H, et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants[J]. Chin Med J(Engl), 2022, 135( 5): 584- 590. DOI: 10.1097/CM9.0000000000002108.
    OMATA M, CHENG AL, KOKUDO N, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update[J]. Hepatol Int, 2017, 11( 4): 317- 370. DOI: 10.1007/s12072-017-9799-9.
    MEHTA N, DODGE JL, GRAB JD, et al. National experience on down-staging of hepatocellular carcinoma before liver transplant: Influence of tumor burden, alpha-fetoprotein, and wait time[J]. Hepatology, 2020, 71( 3): 943- 954. DOI: 10.1002/hep.30879.
    PAN HW, OU YH, PENG SY, et al. Overexpression of osteopontin is associated with intrahepatic metastasis, early recurrence, and poorer prognosis of surgically resected hepatocellular carcinoma[J]. Cancer, 2003, 98( 1): 119- 127. DOI: 10.1002/cncr.11487.
    OKUDA H, NAKANISHI T, TAKATSU K, et al. Clinicopathologic features of patients with hepatocellular carcinoma seropositive for alpha-fetoprotein-L3 and seronegative for des-gamma-carboxy prothrombin in comparison with those seropositive for des-gamma-carboxy prothrombin alone[J]. J Gastroenterol Hepatol, 2002, 17( 7): 772- 778. DOI: 10.1046/j.1440-1746.2002.02806.x.
    CARR BI, KANKE F, WISE M, et al. Clinical evaluation of lens culinaris agglutinin-reactive alpha-fetoprotein and des-gamma-carboxy prothrombin in histologically proven hepatocellular carcinoma in the United States[J]. Dig Dis Sci, 2007, 52( 3): 776- 782. DOI: 10.1007/s10620-006-9541-2.
    AHN JC, TENG PC, CHEN PJ, et al. Detection of circulating tumor cells and their implications as a biomarker for diagnosis, prognostication, and therapeutic monitoring in hepatocellular carcinoma[J]. Hepatology, 2021, 73( 1): 422- 436. DOI: 10.1002/hep.31165.
    CHEN VL, XU D, WICHA MS, et al. Utility of liquid biopsy analysis in detection of hepatocellular carcinoma, determination of prognosis, and disease monitoring: a systematic review[J]. Clin Gastroenterol Hepatol, 2020, 18( 13): 2879- 2902. DOI: 10.1016/j.cgh.2020.04.019.
    DU D, LIU C, QIN M, et al. Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma[J]. Acta Pharm Sin B, 2022, 12( 2): 558- 580. DOI: 10.1016/j.apsb.2021.09.019.
    DE MATTEIS S, RAGUSA A, MARISI G, et al. Aberrant metabolism in hepatocellular carcinoma provides diagnostic and therapeutic opportunities[J]. Oxid Med Cell Longev, 2018, 2018: 7512159. DOI: 10.1155/2018/7512159.
    LIU J, GENG W, SUN H, et al. Integrative metabolomic characterisation identifies altered portal vein serum metabolome contributing to human hepatocellular carcinoma[J]. Gut, 2022, 71( 6): 1203- 1213. DOI: 10.1136/gutjnl-2021-325189.
    DONG TS, JACOBS JP, AGOPIAN V, et al. Duodenal microbiome and serum metabolites predict hepatocellular carcinoma in a multicenter cohort of patients with cirrhosis[J]. Dig Dis Sci, 2022, 67( 8): 3831- 3841. DOI: 10.1007/s10620-021-07299-2.
    YE G, ZHU B, YAO Z, et al. Analysis of urinary metabolic signatures of early hepatocellular carcinoma recurrence after surgical removal using gas chromatography-mass spectrometry[J]. J Proteome Res, 2012, 11( 8): 4361- 4372. DOI: 10.1021/pr300502v.
    GEYER T, RÜBENTHALER J, ALUNNI-FABBRONI M, et al. NMR-based lipid metabolite profiles to predict outcomes in patients undergoing interventional therapy for a hepatocellular carcinoma(HCC): A substudy of the SORAMIC trial[J]. Cancers(Basel), 2021, 13( 11): 2787. DOI: 10.3390/cancers13112787.
    CASADEI-GARDINI A, DEL COCO L, MARISI G, et al. 1H-NMR based serum metabolomics highlights different specific biomarkers between early and advanced hepatocellular carcinoma stages[J]. Cancers(Basel), 2020, 12( 1): 241. DOI: 10.3390/cancers12010241.
    WANG Q, SU B, DONG L, et al. Liquid chromatography-mass spectrometry-based nontargeted metabolomics predicts prognosis of hepatocellular carcinoma after curative resection[J]. J Proteome Res, 2020, 19( 8): 3533- 3541. DOI: 10.1021/acs.jproteome.0c00344.
    FANG C, SU B, JIANG T, et al. Prognosis prediction of hepatocellular carcinoma after surgical resection based on serum metabolic profiling from gas chromatography-mass spectrometry[J]. Anal Bioanal Chem, 2021, 413( 12): 3153- 3165. DOI: 10.1007/s00216-021-03281-z.
    HAN J, HAN ML, XING H, et al. Tissue and serum metabolomic phenotyping for diagnosis and prognosis of hepatocellular carcinoma[J]. Int J Cancer, 2020, 146( 6): 1741- 1753. DOI: 10.1002/ijc.32599.
    NENU I, STEFANESCU H, PROCOPET B, et al. Navigating through the lipid metabolism maze: diagnosis and prognosis metabolites of hepatocellular carcinoma versus compensated cirrhosis[J]. J Clin Med, 2022, 11( 5): 1292. DOI: 10.3390/jcm11051292.
    LU D, YANG F, LIN Z, et al. A prognostic fingerprint in liver transplantation for hepatocellular carcinoma based on plasma metabolomics profiling[J]. Eur J Surg Oncol, 2019, 45( 12): 2347- 2352. DOI: 10.1016/j.ejso.2019.07.004.
    NG S, JANG GH, KURLAND IJ, et al. Plasma metabolomic profiles in liver cancer patients following stereotactic body radiotherapy[J]. EBioMedicine, 2020, 59: 102973. DOI: 10.1016/j.ebiom.2020.102973.
    MAZZAFERRO V, REGALIA E, DOCI R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis[J]. N Engl J Med, 1996, 334( 11): 693- 699. DOI: 10.1056/NEJM199603143341104.
    CHENG YR, YAN D, YANG JD, et al. Effect of transcatheter arterial chemoembolization combined with sorafenib in the treatment of primary liver cancer and its impact on patients’ immune function[J]. Clin J Med Offic, 2021, 49( 3): 290- 291. DOI: 10.16680/j.1671-3826.2021.03.16.

    程瑜蓉, 严冬, 杨建东, 等. 肝动脉栓塞化疗联合索拉非尼在原发性肝癌治疗中应用效果及对患者免疫功能影响[J]. 临床军医杂志, 2021, 49( 3): 290- 291. DOI: 10.16680/j.1671-3826.2021.03.16.
    FAN J, GAO Q. Immunotherapy for hepacellular carcinoma: where there is hope, there is brightness[J]. Chin J Dig Surg, 2022, 21( 2): 199- 204. DOI: 10.3760/cma.j.cn115610-20220215-00080.

    樊嘉, 高强. 肝癌的免疫治疗: 有希望便是光明[J]. 中华消化外科杂志, 2022, 21( 2): 199- 204. DOI: 10.3760/cma.j.cn115610-20220215-00080.
    LIANG J, LI L. Progress and consideration of immunotherapy strategy for hepatocellular carcinoma[J]. Chin J Dig Surg, 2021, 20( 2): 184- 190. DOI: 10.3760/cma.j.cn115610-20201228-00809.

    梁军, 李丽. 肝癌免疫治疗策略的进展与思考[J]. 中华消化外科杂志, 2021, 20( 2): 184- 190. DOI: 10.3760/cma.j.cn115610-20201228-00809.
    HEBERER M, TALKE H, MAIER KP, et al. Metabolism of phenylalanine in liver diseases[J]. Klin Wochenschr, 1980, 58( 21): 1189- 1196. DOI: 10.1007/BF01478875.
    YANG Y, LI C, NIE X, et al. Metabonomic studies of human hepatocellular carcinoma using high-resolution magic-angle spinning 1H NMR spectroscopy in conjunction with multivariate data analysis[J]. J Proteome Res, 2007, 6( 7): 2605- 2614. DOI: 10.1021/pr070063h.
    BIZZARRI M, DINICOLA S, BEVILACQUA A, et al. Broad Spectrum Anticancer Activity of Myo-Inositol and Inositol Hexakisphosphate[J]. Int J Endocrinol, 2016, 2016: 5616807. DOI: 10.1155/2016/5616807.
    THOMAS CE, LUU HN, WANG R, et al. Association between Pre-Diagnostic Serum Bile Acids and Hepatocellular Carcinoma: The Singapore Chinese Health Study[J]. Cancers(Basel), 2021, 13( 11): 2648. DOI: 10.3390/cancers13112648.
    SUN WB, LIU XL, LI W. Research advances in metabolic markers for hepatocellular carcinoma[J]. J Clin Hepatol, 2018, 34( 6): 1318- 1324. DOI: 10.3969/j.issn.1001-5256.2018.06.040.

    孙文博, 刘相良, 李薇. 肝细胞癌代谢标志物的研究进展[J]. 临床肝胆病杂志, 2018, 34( 6): 1318- 1324. DOI: 10.3969/j.issn.1001-5256.2018.06.040.
    FORMELLI F, MENEGHINI E, CAVADINI E, et al. Plasma retinol and prognosis of postmenopausal breast cancer patients[J]. Cancer Epidemiol Biomarkers Prev, 2009, 18( 1): 42- 48. DOI: 10.1158/1055-9965.EPI-08-0496.
    MONDUL AM, WATTERS JL, MÄNNISTÖ S, et al. Serum retinol and risk of prostate cancer[J]. Am J Epidemiol, 2011, 173( 7): 813- 821. DOI: 10.1093/aje/kwq429.
    LU W, SU X, KLEIN MS, et al. Metabolite measurement: pitfalls to avoid and practices to follow[J]. Annu Rev Biochem, 2017, 86: 277- 304. DOI: 10.1146/annurev-biochem-061516-044952.
    XIA H, CHEN J, SEKAR K, et al. Clinical and metabolomics analysis of hepatocellular carcinoma patients with diabetes mellitus[J]. Metabolomics, 2019, 15( 12): 156. DOI: 10.1007/s11306-019-1619-x.
    CAO LL, HAN Y, WANG Y, et al. Metabolic profiling identified a novel biomarker panel for metabolic syndrome-positive hepatocellular cancer[J]. Front Endocrinol(Lausanne), 2021, 12: 816748. DOI: 10.3389/fendo.2021.816748.
    ASSI N, GUNTER MJ, THOMAS DC, et al. Metabolic signature of healthy lifestyle and its relation with risk of hepatocellular carcinoma in a large European cohort[J]. Am J Clin Nutr, 2018, 108( 1): 117- 126. DOI: 10.1093/ajcn/nqy074.
  • 加载中


    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索


    Article Metrics

    Article views (262) PDF downloads(42) Cited by()
    Proportional views


    DownLoad:  Full-Size Img  PowerPoint