Interferon-lambda ( IFNL ) germline variations and their significance for HCC and PDAC progression: an analysis of The C
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RESEARCH ARTICLE
Open Access
Interferon-lambda (IFNL) germline variations and their significance for HCC and PDAC progression: an analysis of The Cancer Genome Atlas (TCGA) data Henriette Huschka and Sabine Mihm*
Abstract Background: Hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC) are malignancies with a leading lethality. With reference to interferons (IFNs) known to mediate antitumor activities, this study investigated the relationship between germline genetic variations in type III IFN genes and cancer disease progression from The Cancer Genome Atlas (TCGA) data. The genetic variations under study tag a gain-or-loss-offunction dinucleotide polymorphism within the IFNL4 gene, rs368234815 [TT/ΔG]. Methods: The entirety of the TCGA sequencing data was used to assess genotypes of 187 patients with HCC and of 162 patients with PDAC matched for ethnicity. Stratified for IFNL genotypes, both cohorts were subjected to time-to-event analyses according to Kaplan-Meier with regard to the length of the specific progression free interval (PFI) and the overall survival (OS) time as two clinical endpoints for disease progression. Results: Logrank analysis revealed a significant relationship between IFNL genotypes and disease outcome for PDAC. This relationship was not found for HCC. A multiple Cox regression analysis employing patients’ age, tumor grade and tumor stage as further covariates proved IFNL genotypes to be independent predictors for PDAC disease outcome. Conclusion: This repository-based approach unveiled clinical evidence suggestive for an impact of IFNL germline variations for PDAC progression with an IFNL haplotype predisposing for IFNL4 expression being favorable. Keywords: Interferon-lambda4 (IFNL4), IFNL4 rs368234815, Type III interferons, Hepatocellular carcinoma (HCC), Pancreatic ductal adenocarcinoma (PDAC), Antitumor host response, Progression free interval (PFI), Overall survival (OS)
Background Hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC) are leading causes of cancerrelated deaths [1]; they belong to the most lethal malignancies with 5-yr survival rates < 20% [2, 3]. According to Hanahan and Weinberg, dysregulated cellular * Correspondence: [email protected] Department of Gastroenterology, Gastrointestinal Oncology, and Endocrinology, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany
pathways that transform growth of normal cells into neoplasms are regarded as ‘hallmarks of cancer’ [4]. The evasion of the host’s immune defense, later on, has been recognized as one further principle of promoting malignant growth [4]. The impact of the host’s immune system for disease progression is underscored by the recent successful clinical translation of immunotherapeutic strategies [5]. Understanding that not all patients benefit from cancer immunotherapy, the term ‘cancer immune responsiveness’
© The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International Li
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