Integrated transcriptome and single-cell RNA sequencing analysis revealed the prognostic significance of GBP4 in pancreatic adenocarcinoma

Abstract

Background

The role of GBP4 in cancer has been preliminarily identified, yet its specific function in patients with pancreatic adenocarcinoma (PAAD) remains unclear. The aim of this study is to determine the impact of the GBP4 gene on PAAD.

Methods

Transcriptomics and single-cell RNA sequencing (scRNA-seq) data were obtained from public databases. Prognostic genes were screened using univariate Cox and least absolute shrinkage and selection operator (LASSO) regression to construct and validate the model. Pathway enrichment and immune microenvironment analyses explored PAAD mechanisms, while scRNA-seq revealed key cell populations and dynamic gene expression. Functional experiments of GBP4 on tumor cell growth were investigated in vitro and in vivo.

Results

This study identified 5 prognostic genes related to the GBP4 gene in PAAD, including GBP2, KRT6A, MMP7, BCAT1, and SPRR1A. The risk model showed validity and generalizability, with "cell cycle" pathway enrichment in high-risk groups and metabolic pathways in low-risk groups. Immune cell infiltration (e.g., central memory CD8 T cells, activated B cells) differed significantly between risk groups (p < 0.01) and correlated with prognostic genes. Ductal cells were key cells, with prognostic gene expression varying during differentiation. In vitro functional assays confirmed the role of GBP4 in promoting pancreatic cancer cell proliferation, migration, and invasion. Moreover, silencing of GBP4 inhibited tumor growth in vivo, whereas GBP4 overexpression increased the tumor growth.

Conclusion

This study identifies GBP4-related prognostic genes and demonstrates the role of GBP4 in pancreatic cancer progression, providing new perspectives for prognostic prediction and therapeutic targeting.