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Hepatic IFNL4 Gene Activation in Hepatocellular Carcinoma Patients with Regard to Etiology

Department of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center, 37075 Goettingen, Germany
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Author to whom correspondence should be addressed.
Academic Editors: Takumi Kawaguchi and Giuliano Ramadori
Int. J. Mol. Sci. 2021, 22(15), 7803; https://doi.org/10.3390/ijms22157803
Received: 16 May 2021 / Revised: 16 July 2021 / Accepted: 19 July 2021 / Published: 21 July 2021
(This article belongs to the Special Issue Gene-Expression in Liver Cells in Health and Disease)
Hepatocellular carcinoma (HCC) is a malignancy with a leading lethality. The etiology is quite diverse, ranging from viral infections to metabolic disorders or intoxications, and associates with specific somatic mutational patterns and specific host immunological phenotypes. Particularly, hepatitis C virus (HCV)-infected liver is featured by an activation of interferon (IFN)-stimulated genes (ISGs; IFN signature), which we suppose is driven by type III IFNL4. Taking advantage of the TCGA collection of HCC patients of various different etiologies, this study aimed at validating our previous findings on hepatic IFNL4 gene activation in HCV infection in an independent and larger cohort of patients with advanced liver disease. In a cohort of n = 377 cases, the entirety of the sequencing data was used to assess the IFNL genotypes, and the cases were stratified for etiology. The number of IFNL4 transcripts within nonmalignant and malignant tissues was found to be more abundant in patients with HCV or HCV/HBV infections when compared to other risk factors. Moreover, in patients with HCV infection as a risk factor, a close, positive relationship was found between ISG activation and the number of functional IFNL4 transcripts. Data on this independent TCGA sample support the concept of an IFNL4-dependent HCV-driven activation of hepatic ISGs. In addition to that, they add to the understanding of etiology-related host immunological phenotypes in HCC. View Full-Text
Keywords: hepatitis C virus (HCV); hepatocellular carcinoma (HCC); interferon-stimulated gene (ISG); interferon lambda 4 (IFNL4); rs368234815; rs11322783; The Cancer Genome Atlas (TCGA) hepatitis C virus (HCV); hepatocellular carcinoma (HCC); interferon-stimulated gene (ISG); interferon lambda 4 (IFNL4); rs368234815; rs11322783; The Cancer Genome Atlas (TCGA)
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MDPI and ACS Style

Huschka, H.; Mihm, S. Hepatic IFNL4 Gene Activation in Hepatocellular Carcinoma Patients with Regard to Etiology. Int. J. Mol. Sci. 2021, 22, 7803. https://doi.org/10.3390/ijms22157803

AMA Style

Huschka H, Mihm S. Hepatic IFNL4 Gene Activation in Hepatocellular Carcinoma Patients with Regard to Etiology. International Journal of Molecular Sciences. 2021; 22(15):7803. https://doi.org/10.3390/ijms22157803

Chicago/Turabian Style

Huschka, Henriette, and Sabine Mihm. 2021. "Hepatic IFNL4 Gene Activation in Hepatocellular Carcinoma Patients with Regard to Etiology" International Journal of Molecular Sciences 22, no. 15: 7803. https://doi.org/10.3390/ijms22157803

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