Background: The role of guanylate-binding proteins (GBPs) in various cancers has been elucidated recently. However, our knowledge of the clinical relevance and biological characteristics of GBPs in hepatocellular carcinoma (HCC) remains limited.
Methods: A total of 955 HCC patients were enrolled from five independent public HCC cohorts. The role of GBP molecules in HCC was preliminarily investigated, and a GBP family signature, termed GBPs-score, was constructed by principal component analysis to combine the GBP molecule values. We revealed the effects of GBP genes and GBPs-score in HCC via well-established bioinformatics methods and validated GBP1-5 experimentally in a tissue microarray (TMA) cohort.
Results: GBPs molecules were closely associated with the prognosis of patients with HCC, and a high GBPs-score highly inferred a favorable survival outcome. We also revealed high GBPs-score was related to anti-tumor immunity, the immune-hot tumor microenvironment (TME), and immunotherapy response. Among the GBPs members, GBP1-5 rather than GBP6/7 may be dominant in these fields. The TMA analysis based on immunohistochemistry showed positive correlations between GBP1-5 and the immune-hot TME with abundant infiltration of CD8+ T cells in HCC.
Conclusions: Our integrative study revealed the genetic and immunologic characterizations of GBPs in HCC and highlighted their potential values as promising biomarkers for prognosis and immunotherapy.
Keywords: guanylate-binding proteins; hepatocellular carcinoma; immunotherapy; tumor microenvironment.
© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.