Guanylate‐binding proteins signature predicts favorable prognosis, immune‐hot microenvironment, and immunotherapy response in hepatocellular carcinoma

作者：Yumei Ning, Shilin Fang, Jun Fang, Kun Lin, Haihang Nie, Peiling Xiong, Peishan Qiu, Qiu Zhao, Haizhou Wang, Fan Wang · 发表于：Cancer Medicine · 年份：2023 · DOI：10.1002/cam4.6347 · 被引用次数：10 · 研究领域：Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis、Hepatocellular Carcinoma Treatment and Prognosis

Abstract 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.