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World J Gastrointest Oncol. Oct 15, 2026; 18(10): 122608
Published online Oct 15, 2026. doi: 10.4251/wjgo.122608
Context-dependent prognostic role of neutrophils and mast cells in primary colorectal cancer and liver metastases
Wen-Jing Ye, Esraa Ali, Sergii Pavlov, Lenka Červenková, Filip Ambrozkiewicz, Ondřej Vyčítal, Petr Hošek, Ondřej Daum, Václav Liška, Kari Hemminki, Andriy Trailin
Wen-Jing Ye, Esraa Ali, Sergii Pavlov, Filip Ambrozkiewicz, Kari Hemminki, Andriy Trailin, Laboratory of Translational Cancer Genomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen 32300, Czech Republic
Lenka Červenková, Ondřej Vyčítal, Petr Hošek, Ondřej Daum, Václav Liška, Laboratory of Cancer Treatment and Tissue Regeneration, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen 32300, Czech Republic
Ondřej Vyčítal, Václav Liška, Department of Surgery, Pilsen University Hospital and Faculty of Medicine in Pilsen, Charles University, Pilsen 32300, Czech Republic
Ondřej Daum, The Department of Pathology, Regional Hospital Liberec, Liberec 46001, Czech Republic
Kari Hemminki, Department of Cancer Epidemiology, German Cancer Research Center, Heidelberg 69120, Germany
Author contributions: Ye WJ was responsible for data curation, formal analysis and writing original draft as first author; Pavlov S, Červenková L, Ambrozkiewicz F, Vyčítal O, Daum O and Trailin A were responsible for data curation and methodology; Pavlov S, Červenková L, Ambrozkiewicz F, Vyčítal O, and Trailin A were responsible for formal analysis; Liška V and Hemminki K were responsible for resources, funding acquisition, and project administration; Liška V, Hemminki K, and Trailin A were responsible for validation and review and editing; Hemminki K and Trailin A were responsible for conceptualization and supervision; and all authors have read and agreed to the published version of the manuscript.
AI contribution statement: Portions of this manuscript were edited using AI tools solely for language refinement. The authors carefully reviewed and verified all AI-assisted outputs and take full responsibility for the scientific content of the manuscript.
Supported by Ministry of Health of Czech Republic, No. NU21-03-00506 and No. NW24-03-00521; SALVAGE Project (OP JAK; co-financed by the European Union and the State Budget of the Czech Republic), No. CZ.02.01.01/00/22_008/0004644; Cooperatio Program, Research Area SURG; and Integration of Biomedical Research and Health Care in the Pilsen Metropolitan Area (co-funded by the European Union and by the State Budget of the Czech Republic), No. CZ.02.01.01/00/23_021/0008828.
Institutional review board statement: The study was approved by the Ethics Committee of the Pilsen University Hospital and Faculty of Medicine in Pilsen (300/20, 17 June 2020).
Informed consent statement: The need for informed consent was waived by the Ethics Committee of the Pilsen University Hospital and Faculty of Medicine in Pilsen.
Conflict-of-interest statement: All authors declare that they have no conflicts of interest.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Data sharing statement: All data generated or analyzed during this study are included in this article and its additional material files. Further enquiries can be directed to the corresponding author.
Corresponding author: Andriy Trailin, MD, Laboratory of Translational Cancer Genomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1665/76, Pilsen 32300, Czech Republic.
andriy.trailin@lfp.cuni.cz
Received: April 23, 2026
Revised: June 15, 2026
Accepted: August 5, 2026
Published online: October 15, 2026
Processing time: 149 Days and 6.5 Hours
BACKGROUND
Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Liver metastases (LM) are a major prognostic factor affecting survival and treatment outcomes. Distinguishing between synchronous and metachronous metastases is clinically important due to differences in tumor biology, immune contexture, and prognosis. Polymorphonuclear neutrophils (PMNs) and mast cells (MCs) are innate immune effectors that influence CRC progression and metastasis. However, their distribution across primary CRC (pCRC), adjacent non-tumor mucosa (NM), and LM, and prognostic relevance remain incompletely understood.
AIM
To evaluate distribution and prognostic value of PMNs and MCs in NM, pCRC, and LM in synchronous and metachronous CRC.
METHODS
This exploratory retrospective cohort study included patients undergoing resection of pCRC with NM and synchronous LM (stage IV, n = 55) or metachronous LM (stage I-III, n = 44). CD66b+ PMNs and CD117+ MCs were assessed using immunohistochemistry, whole-slide imaging, and QuPath-based quantification across NM, tumor center (TC), inner margin (IM) and outer margin (OM), and peritumor zone (PT) of pCRC and LM. Cell densities were compared by site, region, and timing of metastatic presentation, and associated with disease-free survival (DFS).
RESULTS
PMNs were enriched in pCRC compared to NM, whereas MCs predominated in NM. Greater densities of PMNs and MCs were found in LM and pCRC, respectively. High PMNs in OM (HR = 2.40, 95%CI: 1.14-5.04, P = 0.021) and PT (HR = 2.58, 95%CI: 1.22-5.46, P = 0.013) of synchronous LM and OM of pCRC in stage I-III (HR = 2.59, 95%CI: 1.11-6.02, P = 0.027) correlated with shorter DFS, whereas high PMNs in TC of metachronous LM predicted longer DFS (HR = 0.48, 95%CI: 0.24-0.99, P = 0.048). High MC density in TC of pCRC in stage I-III predicted shorter DFS (HR = 2.34, 95%CI: 1.05-5.23, P = 0.038). These exploratory findings require validation in independent cohorts.
CONCLUSION
PMN density increased from NM to LM, while MCs decreased. MCs showed protumor prognostic associations in pCRC; PMNs were protumor in stage I-III pCRC and synchronous LM, but antitumor in metachronous LM.
Core Tip: Densities of polymorphonuclear neutrophils (PMNs) and mast cells (MCs) showed distinct spatial patterns across colorectal cancer (CRC) progression, with PMNs increasing and MCs decreasing from nontumor mucosa through primary CRC (pCRC) to liver metastases (LM). MCs in pCRC exhibited protumor associations with survival, whereas PMNs showed context-dependent survival associations, being unfavorable in stage I-III pCRC and synchronous LM but favorable in metachronous LM. These findings highlight dynamic, stage- and site-specific roles of PMNs and MCs and after validation may serve as prognostic biomarkers for CRC patients.
