The Role of Cytokines in the Different Stages of Hepatocellular Carcinoma
1
Department of Medicine, Division of Gastroenterology & Division of Infectious Disease, University of Minnesota, Minneapolis, MN 55455, USA
2
Department of Gastroenterology and Hepatology, Erasmus MC, 3015 CE Rotterdam, The Netherlands
3
Health Partners Digestive Care, Saint Paul, MN 55130, USA
*
Author to whom correspondence should be addressed.
Cancers 2021, 13(19), 4876; https://doi.org/10.3390/cancers13194876
Submission received: 21 August 2021
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Revised: 23 September 2021
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Accepted: 27 September 2021
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Published: 29 September 2021
(This article belongs to the Special Issue Management of Hepatocellular Carcinoma in Liver Disease)
Simple Summary
Non-homeostatic cytokine expression during hepatocellular carcinogenesis, together with simple and inexpensive cytokine detection techniques, has opened up its use as potential biomarkers, from cancer detection to prognosis. However, carcinogenic programs during cancer progression are not linear. Therefore, cytokines with prognostic potential in one stage may not be relevant in another. Here, we reviewed cytokines with clinical potential in different settings during hepatocellular carcinoma progression.
Abstract
Hepatocellular carcinoma (HCC) is the primary form of liver cancer and a leading cause of cancer-related death worldwide. Early detection remains the most effective strategy in HCC management. However, the spectrum of underlying liver diseases preceding HCC, its genetic complexity, and the lack of symptomatology in early stages challenge early detection. Regardless of underlying etiology, unresolved chronic inflammation is a common denominator in HCC. Hence, many inflammatory molecules, including cytokines, have been investigated as potential biomarkers to predict different stages of HCC. Soluble cytokines carry cell-signaling functions and are easy to detect in the bloodstream. However, its biomarkers’ role remains limited due to the dysregulation of immune parameters related to the primary liver process and their ability to differentiate carcinogenesis from the underlying disease. In this review, we discuss and provide insight on cytokines with clinical relevance for HCC differentiating those implicated in tumor formation, early detection, advanced disease, and response to therapy.
