Immune-metabolic Crosstalk Driven by Pyroptosis in Colorectal Cancer: Identification of an Immunoregulatory Prognostic Signature and Mechanistic Pathways
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Daoli Liu
,
Bohuang Zeng
,
Yuming Gong
,
Jian Wang
,
Donghua Gao
,
Yangfen He
,
Yi Zhou
,
Jiayi Wu
,
Rong Zhang
,
Huajing Long
Abstract
Pyroptosis is an inflammatory form of programmed cell death involved in antitumor immunity and tumor microenvironment regulation. However, its relationships with immune signaling and metabolic adaptation in colorectal cancer (CRC) remain incompletely understood.
An integrated bioinformatics analysis was performed using Gene Expression Omnibus datasets GSE20916 and GSE73360 and The Cancer Genome Atlas colorectal adenocarcinoma cohort. Pyroptosis- and glucose metabolism-related genes were retrieved from public databases and the literature. Differential expression, functional enrichment, Cox regression, least absolute shrinkage and selection operator modeling, gene set enrichment and variation analyses, and protein–protein interaction analyses were conducted.
Fifty-six pyroptosis- and metabolism-related differentially expressed genes were identified. Enrichment analyses highlighted immune and inflammatory pathways, including IL-17 signaling, cytokine-mediated responses, neutrophil extracellular trap formation, chemokine receptor interactions, and IL-10 signaling. A seven-gene prognostic signature comprising ELANE, BRCA1, FKBP10, H1-5, CXCL8, GATA1, and FNDC5 was established, with receiver operating characteristic areas under the curve exceeding 0.90. Risk-stratified analyses revealed enrichment of Wnt/β-catenin and Notch signaling, suggesting associations between immune regulation and metabolic adaptation. Protein–protein interaction analysis identified CXCL8, ELANE, BRCA1, GATA1, and FNDC5 as hub genes potentially involved in tumor-associated immune remodeling.
These findings suggest interconnected pyroptosis, immune, and metabolic processes in CRC and identify a prognostic signature with potential biomarker value. Inflammatory cytokine signaling and Wnt/Notch-associated pathways warrant further investigation to clarify their mechanistic roles and relevance to immunotherapeutic stratification.
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| Issue | Articles in Press | |
| Section | Original Article(s) | |
| Keywords | ||
| Colorectal cancer Cytokine signaling Immune-metabolic reprogramming Prognostic signature Pyroptosis Tumor immunology | ||
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