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Biomarkers Associated with Adiposity and Metabolic Dysfunction in Hepatobiliary Tract Cancer

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Biomarkers in Liver Disease

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Abstract

There is ample evidence implicating obesity, nonalcoholic fatty liver disease, and associated metabolic disorders in the risk of hepatobiliary tract cancer. A number of circulating biomarkers related to obesity and metabolic dysfunction could serve as (1) reliable proxies for adiposity-associated disease risk, (2) indicators of intermediate phenotypic alterations, and (3) early markers of elevated disease risk. This book chapter is aimed at providing an overview of recent advances linking biomarkers associated with obesity and impaired metabolism with hepatobiliary tract cancer development and progression. Here, we largely focus on the role of selected metabolic biomarkers – both established and novel ones – as potential intermediates of the association between obesity and liver cancer risk by means of understanding etiology and improving prevention. Overall, evidence has emerged to suggest circulating biomarkers indicative of hyperinsulinemia, biomarkers of chronic low-grade inflammation and immune response, and selected adipose tissue-derived cytokines and hormones to be associated with the risk of the most common form of liver cancer – hepatocellular carcinoma. Moreover, recent evidence largely supports the role of metabolic biomarkers as early disease risk predictors in “low-risk” population groups such as Western Europe and North America. Novel “omics” technologies – metabolomics, proteomics, and glycomics – are intensively being used for the identification of biomarkers in the metabolic pathways. Targeted and untargeted metabolomic approaches have recently led to the discovery of metabolites representing key metabolic alterations in amino acid, polyunsaturated lipid, acetate, and citrate metabolism in the development of liver cancer. Furthermore, metabolic biomarkers were shown to improve primary liver cancer diagnosis beyond the most common biomarkers applied in clinical practice – i.e., alpha-fetoprotein and liver enzyme levels. The role of obesity and metabolic biomarkers was also suggested for gallbladder cancer; however these links remain largely uninvestigated. Despite the given promise for biomarker application, further research is warranted in order to better characterize specific metabolic biomarkers in understanding etiology and their validation as early markers for risk assessment of hepatobiliary tract cancer.

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Abbreviations

BMI:

Body mass index

EPIC:

European Prospective Investigation into Cancer and Nutrition Cohort

HCC:

Hepatocellular carcinoma

HOMA-IR index:

Homeostasis model assessment of insulin resistance index

IGF:

Insulin-like growth factor

IGFBP:

Insulin-like growth factor binding protein

IL-6:

Interleukin-6

NAFLD:

Nonalcoholic fatty liver disease

NASH:

Nonalcoholic steatohepatitis

TNF-a:

Tumor necrosis factor-alpha

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Authors and Affiliations

  1. Nutrition, Immunity and Metabolism Start-up Lab, Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Arthur-Scheunert Allee 114-116, 14558, Nuthetal, Germany

    Krasimira Aleksandrova

  2. Institut für Epidemiologie, Christian-Albrechts-Universität zu Kiel, UKSH, Campus Kiel, Haus 1, Niemannsweg 11, 24105, Kiel, Germany

    Sabrina Schlesinger

  3. Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Arthur-Scheunert Allee 114-116, 14558, Nuthetal, Germany

    Marta Stelmach-Mardas

  4. Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Szpitalna Str 27/33, 60-537, Poznan, Poland

    Marta Stelmach-Mardas

  5. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St. Mary’s Campus, Norfolk Place, Paddington, W2 1PG, London, UK

    Sabrina Schlesinger

Authors
  1. Krasimira Aleksandrova
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  2. Sabrina Schlesinger
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  3. Marta Stelmach-Mardas
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Correspondence to Krasimira Aleksandrova , Sabrina Schlesinger or Marta Stelmach-Mardas .

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Editors and Affiliations

  1. Sciences Division, King's College, London, United Kingdom

    Victor R. Preedy

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Aleksandrova, K., Schlesinger, S., Stelmach-Mardas, M. (2016). Biomarkers Associated with Adiposity and Metabolic Dysfunction in Hepatobiliary Tract Cancer. In: Preedy, V. (eds) Biomarkers in Liver Disease. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7742-2_37-1

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  • DOI: https://doi.org/10.1007/978-94-007-7742-2_37-1

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