Neutrophil extracellular traps-related signature predicts the prognosis and immune infiltration in gastric cancer

Mingzhe Li; Zidan Zhao; Tsz Kin Mak; Xiaoqun Wang; Jingyao Chen; Hui Ren; Zhiwei Yu; Changhua Zhang

doi:10.3389/fmed.2023.1174764

Neutrophil extracellular traps-related signature predicts the prognosis and immune infiltration in gastric cancer

Front Med (Lausanne). 2023 Aug 10:10:1174764. doi: 10.3389/fmed.2023.1174764. eCollection 2023.

Authors

Mingzhe Li¹, Zidan Zhao¹, Tsz Kin Mak¹, Xiaoqun Wang¹, Jingyao Chen¹, Hui Ren¹, Zhiwei Yu^{1

2}, Changhua Zhang^{1

3}

Affiliations

¹ Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.
² Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, China.
³ Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China.

Abstract

Introduction: Gastric cancer (GC) is the fifth most prevalent cancer globally, with the third highest case fatality rate. Neutrophil extracellular traps (NETs) are a reticulated structure of DNA, histones, and antimicrobial peptides produced by active neutrophils that trap pathogens. Even though NETs are associated with poorer recurrence-free survival (RFS) and overall survival (OS), the specifics of this interaction between NETs and cancer cells are yet unknown.

Methods: The keywords "neutrophil extracellular traps and gastric cancer" were used in the GEO database for retrieval, and the GSE188741 dataset was selected to obtain the NETs-related gene. 27 NETs-related genes were screened by univariate Cox regression analysis (p < 0.05). 27 NETs-related genes were employed to identify and categorize NETs-subgroups of GC patients under the Consensus clustering analysis. 808 GC patients in TCGA-STAD combined with GES84437 were randomly divided into a training group (n = 403) and a test group (n = 403) at a ratio of 1:1 to validate the NETs-related signature.

Results: Based on Multivariate Cox regression and LASSO regression analysis to develop a NETs-related prognosis model. We developed a very specific nomogram to improve the NETs-clinical score's usefulness. Similarly, we also performed a great result in pan-cancer study with NETs-score. Low NETs scores were linked to higher MSI-H (microsatellite instability-high), mutation load, and immune activity. The cancer stem cell (CSC) index and chemotherapeutic treatment sensitivity were also connected to the NET score. Our comprehensive analysis of NETs in GC suggests that NETs have a role in the tumor microenvironment, clinicopathological features, and prognosis.

Discussion: The NETs-score risk model provides a basis for better prognosis and therapy outcomes in GC patients.

Keywords: NETs-related signature; NETs-related signature predicts the prognosis; gastric cancer; immune therapy; neutrophil extracellular traps.