ORIGINAL RESEARCH article
Front. Oncol.
Sec. Gynecological Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1547529
CS Ratio is an immune-related prognostic biomarker for cervical cancer
Provisionally accepted
- 1Tianjin Medical University, Tianjin, China
- 2Nankai University, Tianjin, China
- 3Tianjin Central Hospital for Gynecology and Obstetrics, Tianjin, China
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Background: The tumor microenvironment (TME) plays a crucial role in cancer progression, but its complex structure and significant variability among patients present considerable challenges for research. Recent studies have demonstrated that macrophage polarization states, defined by the expression levels of CXCL9 and SPP1 (CS Ratio), are more prognostically relevant than traditional M1/M2 markers. The CS polarization state reflects a highly coordinated network of pro-tumor and anti-tumor variables, offering a simplified yet effective immune response indicator for the complex TME. The CS Ratio has been shown to correlate with the abundance of anti-tumor immune cells, the gene expression programs of tumor-infiltrating cells, and responses to immunotherapy. Results: The CS Ratio was significantly lower in cervical cancer patients compared to normal controls (P < 0.05). KM survival curves indicated that patients in the CS High group exhibited better prognoses. Immune score analysis revealed significantly higher immune scores (P < 0.05) and lower tumor purity (P < 0.05) in the CS High group compared to the Low group. CIBERSORT analysis revealed significantly higher proportions of CD8+ T cells (P < 0.05) and M1 macrophages (P < 0.05), and a significantly lower proportion of M2 macrophages (P < 0.05), in the CS High group compared to the Low group. The CS Ratio significantly decreased with advancing FIGO stage (P < 0.05). Both univariate (P < 0.05) and multivariate Cox regression analyses (P < 0.05) confirmed the CS Ratio as an independent prognostic factor. ROC analysis demonstrated that the CS Ratio had higher AUC values for predicting 1-year (AUC=0.69), 3-year (AUC=0.66), and 5-year OS (AUC=0.68) than CXCL9 or SPP1 alone. The Cox regression-based nomogram integrating four key features demonstrated predictive capability for 1-, 3-, and 5-year OS in CESC patients (Concordance Index = 0.751; 95% CI: 0.678–0.824; p = 1.50Í10-11). Significant survival differences were observed between the high-risk and low-risk groups based on the nomogram score. ROC analysis yielded high AUC values for survival prediction: 0.85 (95% CI: 0.94-0.75) at 1-year, 0.74 at 3-year, and 0.72 at 5-year. Conclusion: The CS Ratio may serve as a more effective prognostic biomarker for cervical cancer patients.
Keywords: SPP1, CXCL9, Cervical cancer, TCGA, GEO
Received: 18 Dec 2024; Accepted: 04 Aug 2025.
Copyright: © 2025 Shi, Yao, Wang, Yang, Zhang and Qu. 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:
Wenwen Zhang, Tianjin Central Hospital for Gynecology and Obstetrics, Tianjin, China
Pengpeng Qu, Tianjin Medical University, Tianjin, China
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