Hepatic <i>IFNL4</i> Gene Activation in Hepatocellular Carcinoma Patients with Regard to Etiology
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...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-07-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/15/7803 |
| Summary: | 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 <i>IFNL4</i>. Taking advantage of the TCGA collection of HCC patients of various different etiologies, this study aimed at validating our previous findings on hepatic <i>IFNL4</i> gene activation in HCV infection in an independent and larger cohort of patients with advanced liver disease. In a cohort of <i>n</i> = 377 cases, the entirety of the sequencing data was used to assess the <i>IFNL</i> genotypes, and the cases were stratified for etiology. The number of <i>IFNL4</i> 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 <i>IFNL4</i> transcripts. Data on this independent TCGA sample support the concept of an <i>IFNL4</i>-dependent HCV-driven activation of hepatic ISGs. In addition to that, they add to the understanding of etiology-related host immunological phenotypes in HCC. |
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| ISSN: | 1661-6596 1422-0067 |