Mocci Stefano, Perra Andrea, Littera Roberto, Pes Francesco, Melis Maurizio, Sanna Celeste, Mascia Alessia, Murgia Michela, Mereu Caterina, Lorrai Michela, Duś-Ilnicka Irena, Zedda Giorgia, Lai Sara, Giuressi Erika, Guarino Federico, Serra Gianfranco, Miglianti Michela, Stradoni Roberta, Vacca Monica, Zolfino Teresa, Chessa Luchino, Giglio Sabrina
Medical Genetics, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
Center for Research University Services (CeSAR), University of Cagliari, Cagliari, Italy.
Sci Rep. 2025 Apr 17;15(1):13331. doi: 10.1038/s41598-025-97406-4.
Hepatocellular carcinoma (HCC) is the sixth most common cancer globally and the third leading cause of cancer-related mortality, primarily driven by viral infections (HCV, HBV) and steatotic liver diseases (SLD). Despite advances in treatment, early detection and accurate prognosis remain challenging. The Human leukocyte antigen G (HLA-G) molecule is dysregulated in various conditions, including cancers and viral infections. This study aimed to investigate HLA-G's role in viral-related and SLD-driven HCC. We analyzed a cohort of 116 HCC patients and 140 healthy controls to assess HLA-G genetic variants and soluble levels. Results showed significantly higher levels of soluble HLA-G in HCC patients compared to controls (Pc = 0.003). Moreover, overall survival (OS) was significantly lower in patients with the extended HLA-G*01:01:01/UTR-1 haplotype (Log-rank test, p = 0.002), a trend consistent in both HCV and/or HBV-related HCC (p = 0.025) and SLD-related HCC (p = 0.018). Elevated sHLA-G levels were associated with shorter OS across both subgroups (p = 0.034 (HBV/HCV) and p = 0.010 (SLD), respectively). The findings suggest that elevated levels of soluble HLA-G and specific genetic variants are associated with poor prognosis in HCC patients, highlighting the potential of HLA-G as a prognostic biomarker in both viral-related and steatotic liver disease-related HCC.
肝细胞癌（HCC）是全球第六大常见癌症，也是癌症相关死亡的第三大主要原因，主要由病毒感染（HCV、HBV）和脂肪性肝病（SLD）引起。尽管治疗取得了进展，但早期检测和准确预后仍然具有挑战性。人类白细胞抗原G（HLA-G）分子在包括癌症和病毒感染在内的各种情况下都会失调。本研究旨在调查HLA-G在病毒相关和SLD驱动的HCC中的作用。我们分析了116例HCC患者和140例健康对照的队列，以评估HLA-G基因变异和可溶性水平。结果显示，与对照组相比，HCC患者的可溶性HLA-G水平显著更高（Pc = 0.003）。此外，具有扩展的HLA-G*01:01:01/UTR-1单倍型的患者的总生存期（OS）显著更低（对数秩检验，p = 0.002），这一趋势在HCV和/或HBV相关的HCC（p = 0.025）和SLD相关的HCC（p = 0.018）中均一致。在两个亚组中，sHLA-G水平升高均与较短的OS相关（分别为p = 0.034（HBV/HCV）和p = 0.010（SLD））。这些发现表明，可溶性HLA-G水平升高和特定基因变异与HCC患者的不良预后相关，突出了HLA-G作为病毒相关和脂肪性肝病相关HCC预后生物标志物的潜力。
