Cross-species upregulation of MAGED2 in liver cancer suggests a role in obesity-driven tumor progression

Bayat, Tara (author), Blagotinšek Cokan, Kaja (author), Rozman, Damjana (author), Fon Tacer, Klementina (author)

Melanoma-associated antigens (MAGEs) are cancer-testis antigens (CTAs) aberrantly expressed in multiple cancer types, including hepatocellular carcinoma (HCC), and associated with aggressive phenotypes. Although MAGE proteins are widely studied as cancer immunotherapy targets, their roles in HCC and the regulation of their expression during liver pathogenesis in mouse models, including dietary effects, remain poorly understood. We analyzed Mage gene expression in liver tissues from 78 C3H/HeJ mice with chronic diet-induced obesity. While type I MAGE genes are frequently expressed in human HCC, we found no evidence of their expression in mouse liver tumors, suggesting species-specific regulation. In contrast, type II Maged2, previously reported to be upregulated in human HCC, was significantly increased in mouse liver tumors. Analysis of human HCC samples from The Cancer Genome Atlas (TCGA) database confirmed MAGED2 upregulation and its association with patient prognosis. Together, these findings identify MAGED2 as a conserved marker of liver cancer in both humans and mice and emphasize the importance of cross-species comparative approaches for selecting appropriate models and accurately interpreting results, particularly for CTAs, which often evolved recently and in a species-specific manner.

• Language: English
• Keywords: cancer-testis antigen, CTA, comparative cancer research, hepatocellular carcinoma, high-fat diet, liver tumors, melanoma-associated antigen, MAGE, obesity
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2026
• Number of pages: 23 str.
• Numbering: Vol. 48, iss. 2, art. 139
• PID: 20.500.12556/RUL-182429
• UDC: 616.36-006:613.25
• ISSN on article: 1467-3045
• DOI: 10.3390/cimb48020139
• COBISS.SI-ID: 277413635
• Publication date in RUL: 11.05.2026

Record is a part of a journal

• Title: Current issues in molecular biology
• Shortened title: Curr. issues mol. biol.
• Publisher: MDPI
• ISSN: 1467-3045
• COBISS.SI-ID: 521769497

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: antigen raka testisov, CTA, primerjalne raziskave raka, hepatocelularni karcinom, prehrana z visoko vsebnostjo maščob, tumorji jeter, z melanomom povezan antigen, MAGE, debelost