ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1587947
The prognostic model based on tumor-associated neutrophils contributes to the stromal landscape and influences metabolic reprogramming in colorectal cancer
Provisionally accepted
- 1Sun Yat-sen Memorial Hospital, Guangzhou, China
- 2The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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Background: The tumour microenvironment (TME) is highly complex and significantly influences cancer prognosis and drug sensitivity. Tumor-associated neutrophils (TANs) play a key role in the TME. In this study, we aimed to investigate the TANs-related markers in colorectal cancer (CRC) and develop an integrated signature for prognostic stratification.Methods: The CRC single-cell RNA sequencing (scRNA-seq) data and RNA-seq data were obtained from TCGA and GEO. A risk score was calculated based on the 18 TAN-associated genes identified in CRC by scRNA-seq data and LASSO regression. Prognosis, stromal and immune infiltration landscape, metabolism, and treatment response were then investigated in the low-and high-risk score clusters using RNA-seq data.Results: Patients with a High-risk score had a significantly worse survival outcome than those with a Low-risk score (p < 0.0001). The prognostic predictive potency of the risk score was validated in both the TCGA validation cohort (p < 0.0001) and the GEO cohort (p < 0.00015). The areas under the curves of 1-, 3-, and 5-year survival were 0.76, 0.74, and 0.70 in the TCGA training set; 0.78, 0.68, and 0.78 in the TCGA validation set; and 0.65, 0.64, and 0.62 in the GEO set. The risk score was related to T, N, and M stages. A prognostic nomogram was constructed, and the predictive accuracy was assessed by calibration curve analysis. Decision curve analysis showed the clinical utility of the nomogram. Furthermore, the High-risk score cluster was significantly associated with the levels of cancer-associated fibroblasts, as well as activity in the transforming growth factor-β and WNT pathway. In depth, the High-risk score cluster exhibited lower levels of amino acid, tricarboxylic acid, and nucleotide metabolism, as well as poorer responses to chemotherapeutic agents such as 5-fluorouracil.Conclusions: This novel TAN subtype, based on 18 prognostic-related genes, could provide new insights into the prognostic stratification and treatment options for CRC.
Keywords: colorectal cancer, Single cell sequencing, Tumor-associated neutrophils, Prognostic stratification, immune microenvironment, metabolic reprogramming
Received: 05 Mar 2025; Accepted: 04 Aug 2025.
Copyright: © 2025 Yin, Jiang, Huang, Luo, Xu and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Liang Xu, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510610, China
Qiong Yang, Sun Yat-sen Memorial Hospital, Guangzhou, China
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