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ORIGINAL RESEARCH ARTICLE

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

Jintao Liang1,2 ,  Yalun Liang1,2 ,  Yimao Wu1,3 ,  Shuai Ren4* ,  Meng-Yao Li1,5*
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1 Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
2 The First School of Clinical Medicine, Guangdong Medical University, Zhanjiang, Guangdong, China
3 The Second School of Clinical Medicine, Guangdong Medical University, Dongguan, Guangdong, China
4 Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
5 Shanghai Key Laboratory of Cancer Systems Regulation and Clinical Translation, Shanghai Jiading District Central Hospital, Shanghai, China
IMO, 025400052 https://doi.org/10.36922/IMO025400052
Received: 1 October 2025 | Revised: 10 December 2025 | Accepted: 24 December 2025 | Published online: 27 February 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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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
Funding
None.
Conflict of interest
Meng-Yao Li is the Youth Editorial Board Member of this journal, but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships influenced the work reported in this paper.
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