Brambilla E, Brambilla DJF, Tregnago AC, Riva F, Pasqualotto FF, Soldera J. Exploring macrophage polarization as a prognostic indicator for colorectal cancer: Unveiling the impact of metalloproteinase mutations. World J Clin Cases 2025; 13(23): 105011 [DOI: 10.12998/wjcc.v13.i23.105011]
Corresponding Author of This Article
Jonathan Soldera, PhD, Tutor, Department of Gastroenterology and Acute Medicine, University of South Wales, Llantwit Road, Pontypridd, Cardiff CF37 1DL, United Kingdom. jonathansoldera@gmail.com
Research Domain of This Article
Oncology
Article-Type of This Article
Retrospective Cohort Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Cases. Aug 16, 2025; 13(23): 105011 Published online Aug 16, 2025. doi: 10.12998/wjcc.v13.i23.105011
Exploring macrophage polarization as a prognostic indicator for colorectal cancer: Unveiling the impact of metalloproteinase mutations
Eduardo Brambilla, Daniel Jun Funatsu Brambilla, Aline Caldart Tregnago, Floriano Riva, Fabio Firmbach Pasqualotto, Jonathan Soldera
Eduardo Brambilla, Clinical Gastroenterology, Universidade de Caxias do Sul, Caxias do Sul 95070-560, Rio Grande do Sul, Brazil
Daniel Jun Funatsu Brambilla, School of Medicine, Universidade de Caxias do Sul, Caxias do Sul 95070-560, Rio Grande do Sul, Brazil
Aline Caldart Tregnago, Floriano Riva, Department of Pathology, Universidade de Caxias do Sul, Caxias do Sul 95070-560, Rio Grande do Sul, Brazil
Fabio Firmbach Pasqualotto, Department of Urology, Universidade de Caxias do Sul, Caxias do Sul 95070-560, Rio Grande do Sul, Brazil
Jonathan Soldera, Department of Gastroenterology and Acute Medicine, University of South Wales, Cardiff CF37 1DL, United Kingdom
Co-first authors: Eduardo Brambilla and Jonathan Soldera.
Author contributions: Brambilla E and Soldera J contribute equally to this study as co-first authors; Brambilla E participated in the study design, writing, data collection, data analysis, and supervision; Brambilla DJF contributed to data collection and drafting the original manuscript; Tregnago AC and Riva F were involved in data collection, analysis, and immunohistochemistry studies; Pasqualotto FF and Soldera J contributed to the study design, drafting the manuscript, and reviewing the final version.
Institutional review board statement: This study was approved by the Ethics Committee of the Universidade de Caxias do Sul under approval number 84709824.5.0000.5341.
Informed consent statement: The requirement for informed consent was waived as this study used retrospective data collected from electronic medical records.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest pertaining to the subject matter discussed in this paper.
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: De-identified data may be shared upon reasonable request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jonathan Soldera, PhD, Tutor, Department of Gastroenterology and Acute Medicine, University of South Wales, Llantwit Road, Pontypridd, Cardiff CF37 1DL, United Kingdom. jonathansoldera@gmail.com
Received: January 13, 2025 Revised: March 24, 2025 Accepted: May 7, 2025 Published online: August 16, 2025 Processing time: 146 Days and 21 Hours
Abstract
BACKGROUND
Macrophages play a crucial role in the tumor microenvironment, displaying remarkable plasticity that allows them to either suppress or promote tumor progression. Their polarization into M1 or M2 phenotypes could have significant prognostic implications, and manipulating this polarization may offer a novel approach to controlling colorectal neoplasms.
AIM
To evaluate the infiltration rates of M1 and M2 macrophages in colorectal neoplasia, specifically comparing cases with and without metalloproteinase mutations. Additionally, it sought to explore potential prognostic factors associated with the disease.
METHODS
The study involved two cohorts of patients diagnosed with colorectal neoplasia: 33 patients with metalloproteinase mutations and 33 without. Macrophage quantity and polarization were assessed using markers indicative of M1 (iNOS) and M2 (CD163, CD206) macrophages. Prognostic factors and survival outcomes related to colorectal cancer (CRC) were also analyzed.
RESULTS
Among the 61 patients, 28 (45.9%) exhibited metalloproteinase mutations, while 33 (54.1%) did not. Tumor staging revealed that 16.9% were in stage I, 34.2% in stage II, 42.4% in stage III, and 8.5% in stage IV. The study recorded 12 patient deaths (19.7%), with 21.2% from the control group and 17.9% from the mutation group. M2 macrophages, identified by CD163 and CD206 markers, had mean counts of 23 and 17, respectively, with standard deviations of 21 and 17. In contrast, M1 macrophages, identified by iNOS, had a mean count of five per site, with a standard deviation of 11.
CONCLUSION
The study found no statistically significant differences in macrophage density between groups, irrespective of metalloproteinase mutation status, age, gender, tumor region, staging, TILS, tumor recurrence, or clinical outcomes. No association was observed between macrophage polarization and CRC prognosis or survival. However, patients with metalloproteinase mutations demonstrated a better survival rate, suggesting a potential protective role of this mutation in colorectal neoplasia.
Core Tip: This study investigates the prognostic significance of macrophage polarization in colorectal cancer (CRC), focusing on patients with and without metalloproteinase mutations. Using M1 (inducible nitric oxide synthase) and M2 (CD163, CD206) markers, macrophage densities were quantified and correlated with survival and clinical outcomes. While no significant differences in macrophage density or polarization were observed between groups, the study highlights a potential protective role of metalloproteinase mutations, as patients harboring these mutations demonstrated improved survival rates. This insight may guide future research into the tumor microenvironment and its implications for CRC prognosis and therapy.
