Melanoma antigen genes A1 and A3 as predictors of treatment response and survival in HCV-associated hepatocellular carcinoma: a prospective study

Abstract Introduction Hepatocellular carcinoma (HCC) accounts for approximately 90% of all primary liver cancers resulting in approximately 830,000 deaths in 2020, making HCC the sixth most common cancer globally. Several members of the Melanoma Antigen Gene (MAGE) family, such as MAGE-A1 and A3 genes of the MAGE I-A subfamily, are abnormally expressed in a variety of cancers including melanomas, colorectal cancer, non-small cell lung cancer, gliomas, HCC, prostate, and breast cancers. In addition, they have been linked to tumor stemness and, therefore, may predict therapeutic response and prognosis. Aim of the study To investigate the expression pattern of MAGE-A1 and A3 genes in HCC patients and to evaluate their prognostic value. Subjects and methods This prospective four-year case-control study was conducted from 2020 to 2024 on 95 subjects classified into three groups. Group (A): Fifty patients with HCC developed on top of hepatitis C virus (HCV) - induced liver cirrhosis, Group (B): 30 patients with post-HCV liver cirrhosis and Group (C): 15 healthy control subjects. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to evaluate the expression of MAGE-A1 and A3 genes in peripheral blood sample after peripheral blood mononuclear cells (PBMCs) isolation. Patients were followed up over 2 years duration for assessment of treatment response. Results At cutoff levels 11.54 and 11.39 MAGE-A1 and MAGE-A3, respectively, could distinguish HCC from liver cirrhosis with area under the curve (AUC) of 0.781 and 0.966, respectively ( P  ≤ 0.001). Regarding treatment response, MAGE-A1 and A3 showed significantly higher expression in patients with progressive disease (16.16 and 17.79, respectively) compared to complete response patients (9.21 and 13.25, respectively). Finally, when assessing overall survival (OS) in HCC patients multivariate analysis showed that independent factors for shorter OS were increased MAGE-A1 (HR: 9.407, P: 0.048), high MAGE-A3 (HR: 9.199, P: 0.042) and elevation of both alpha fetoprotein (AFP) and MAGE-A3 (HR: 10.681, P: 0.039). Conclusion MAGE-A1 and A3 genes can be used as diagnostic and prognostic markers in HCC patients predicting therapeutic response and overall survival.