Neutrophil extracellular traps in gallbladder cancer: Mapping regulatory networks, identifying candidate targets, and characterizing pathway dysregulation

Abstract

Gallbladder cancer (GBC) is an aggressive malignancy with limited therapeutic options. The role of neutrophil extracellular traps (NETs) in GBC remains unexplored. This study performed an integrated bioinformatics analysis using two Gene Expression Omnibus datasets (GSE138109 and GSE276931) to investigate NET-associated molecular mechanisms in GBC. After batch correction, differential expression analysis and weighted gene co‑expression network analysis identified phenotype‑associated modules. Intersection with high‑confidence NET‑related genes revealed 54 core genes linking NETs to GBC. Linear mixed model analysis highlighted significant downregulation of ADAMTS1, GPX3, and MYH11 in tumor tissues. Pathway activity analysis showed the upregulation of cell‑cycle pathways (E2F_TARGETS and G2M_CHECKPOINT) and the downregulation of inflammatory pathways (MYOGENESIS and TNFA_SIGNALING_VIA_NFKB). These findings map a regulatory network through which NETs may influence GBC progression by disrupting extracellular matrix integrity and oxidative balance. The study provides a preliminary framework for mechanistic and therapeutic exploration, aligning with the need for molecularly informed strategies in advanced biliary tract cancer.

Keywords

Gallbladder cancer / Neutrophil extracellular traps / Bioinformatics analysis / ADAMTS1 / GPX3 / Pathway dysregulation / Precision oncology

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