Evidence map›Paper›PMID 42601732›Full record

ArticleMedicine2026

Colorectal cancer molecular subtypes and prognostic models based on NET-related genes and oxidative stress-associated signaling.

Yi Wei, WeiJian Chu, ChunHui Rao, Yan Yang

Abstract read
In one paragraph

Article in Medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Yi WeiDepartment of Proctology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.ORCID 0009-0008-0916-0509
WeiJian ChuDepartment of Proctology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
ChunHui RaoDepartment of Proctology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Yan YangDepartment of Otolaryngology, Banshan Community Health Service Center, Gongshu District, Hangzhou, Zhejiang, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Colorectal cancer (CRC) exhibits marked molecular and microenvironmental heterogeneity, and the TNM staging system alone does not fully explain differences in prognosis or treatment response. Neutrophil extracellular traps (NETs) and oxidative stress participate in inflammatory remodeling, immune regulation, and tumor progression in CRC. However, transcriptomic studies integrating NET-related programs with oxidative stress-associated signaling for molecular stratification and prognostic modeling remain limited. Transcriptome and clinical data from TCGA-COADREAD (training set, 449 tumor and 39 normal samples) and GSE39582 (validation set, 566 tumor and 19 non-tumor samples) were analyzed. Candidate NET-related and oxidative stress-associated genes were collected from GeneCards, Gene Ontology, and published NETosis signatures, and were further restricted by differential expression analysis (|log2FC| > 0.585, adjusted P < .05) and univariate Cox analysis (P < .05). Consensus clustering, survival analysis, immune infiltration analysis, mutation analysis, and oncoPredict-based drug sensitivity modeling were performed. A multigene prognostic model was constructed using LASSO-Cox regression and evaluated in both cohorts. Two molecular subtypes were identified. C1 showed a better prognosis, higher tumor mutational burden, higher immune checkpoint and immunogenicity scores, and an immune-active phenotype. C2 showed poorer survival, enrichment of NET formation and inflammatory pathways, lower relative neutrophil infiltration by CIBERSORT, and predicted sensitivity to JAK, Wnt/β-catenin, proteasome, and cell-cycle checkpoint inhibitors. The prognostic model separated high- and low-risk patients in both the training and validation cohorts, with 1-, 3-, and 5-year area under the curves of 0.698, 0.711, and 0.645 in TCGA-COADREAD and 0.542, 0.578, and 0.569 in GSE39582. This study proposes NET-related CRC molecular subtypes with oxidative stress-associated biological context and develops a transcriptomic risk model with external validation. The findings suggest subtype-specific immune and therapeutic features, while prospective clinical and functional validation is required before clinical translation.

Indexed as

Colorectal NeoplasmsExtracellular TrapsOxidative StressSignal TransductionBiomarkers, TumorGene Expression ProfilingGene Expression Regulation, NeoplasticHumansPrognosisTranscriptomeBiomarkers, Tumorcolorectal cancermolecular subtypesneutrophil extracellular trapsoxidative stressprognostic risk model

Identifiers

PMID42601732
PMCPMC13480840

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.