Guanylate binding protein 4 shapes an inflamed tumor microenvironment and identifies immuno-hot tumors

Purpose: Guanylate binding protein 4 (GBP4) is induced by interferons and various cytokines and has been recognized as functionally relevant in numerous types of human cancers. While the role of GBP4 in cancer has been preliminarily summarized, its correlation with antitumor immunity remains unclear and requires further research.

Methods: First, a comprehensive pan-cancer analysis was conducted, focusing on GBP4's expression patterns and immunological functions. Subsequently, we explored the correlations between GBP4 and immunological features within the tumor microenvironment (TME) in non-small cell lung cancer (NSCLC) patients. Additionally, we examined the relationships between GBP4 and emerging immunobiomarkers, such as N6-methyladenosine (m6A) genes. Moreover, we assessed the utility of GBP4 in predicting the clinical characteristics and treatment responses of patients with NSCLC.

Results: Pan-cancer analysis revealed that GBP4 plays a positive role in most cancer types via the majority of immunomodulators. Furthermore, GBP4 demonstrated positive associations with immunomodulatory factors, tumor-infiltrating immune cells (TIICs) and inhibitory immune checkpoints. Remarkably, the expression of GBP4 was found to be a predictor of significantly enhanced responsiveness to anti-EGFR therapy and immunotherapy.

Conclusions: GBP4 expression profiles offer a promising avenue for identifying highly immunogenic tumors across a wide spectrum of cancers. GBP4 holds potential as a robust pan-cancer biomarker for assessing the immunological characteristics of tumors, with particular relevance to its ability to predict therapeutic responses, notably in the context of anti-EGFR therapy and immunotherapy.