Increased MPO in Colorectal Cancer Is Associated With High Peripheral Neutrophil Counts and a Poor Prognosis: A TCGA With Propensity Score-Matched Analysis

Abstract

BackgroundMyeloperoxidase (MPO) has been demonstrated to be a local mediator of inflammation in tissue damage in various inflammatory diseases. Given its controversial effect on colorectal cancer (CRC), there has been growing interest in investigating the role of this enzyme in CRC. The mechanism underlying MPO activity and CRC progression requires further clarification.MethodsThe expression and function of MPO in CRC were evaluated using TCGA analysis. TCGA, TIMER, and Human Cell Landscape analyses were used to analyze the correlation between MPO expression and neutrophil infiltration in CRC. Spearman’s bivariate correlation analysis was used to verify the correlation between MPO levels in CRC and the peripheral neutrophil count. In the clinical analysis, 8,121 patients who underwent elective surgery for CRC were enrolled in this retrospective cohort study from January 2008 to December 2014. Propensity score matching was used to address the differences in baseline characteristics. The Kaplan–Meier method and Cox regression analysis were used to identify independent prognostic factors in patients with CRC.ResultsMPO was upregulated in CRC tissues, which is related to malignant progression and worse survival in CRC patients from TCGA analysis. MPO was significantly correlated with the infiltration level of neutrophils in CRC in TCGA, TIMER, and Human Cell Landscape analyses. MPO was positively correlated with the peripheral neutrophil count. Data of the 8,121 patients who underwent CRC surgery were available for analysis. After propensity score matching, 3,358 patients were included in each group. Kaplan–Meier survival curves showed that high preoperative neutrophil levels were associated with decreased overall survival (OS; P < 0.001) and disease-free survival (DFS; P = 0.015). The preoperative neutrophil count was an independent risk factor for OS (hazard ratio [HR], 1.157; 95% confidence interval [CI], 1.055–1.268; P = 0.002) and DFS (HR, 1.118; 95% CI, 1.009–1.238; P = 0.033).ConclusionsOur research indicates that increased MPO levels in CRC are significantly correlated with high preoperative neutrophil counts, and both serve as prognostic indicators for worse survival in CRC patients. Our study suggests that neutrophils may be key players in the mechanism linking MPO levels with poor CRC outcomes.

Myeloperoxidase enhances the migration of human choriocarcinoma JEG-3 cells1

“…We found that total MPO within the cells was increased at higher concentrations of MPO. During inflammation, levels of MPO are reported to be elevated (33), but there is no data, to our knowledge, regarding local MPO concentrations around neutrophils following degranulation. We hypothesize that upon activation of neutrophils, there is a high concentration of MPO released in their surrounding environment.…”

Quantitative tissue proteome profile reveals neutrophil degranulation and remodeling of extracellular matrix proteins in early stage gallbladder cancer

“…MPO is a member of the heme peroxidase superfamily and is the most abundant protein expressed by neutrophils. It is reported to generate reactive oxygen species (ROS) leading to DNA damage and mutation inducing carcinogenesis and thus resulting in tissue damage (30). PRTN3 is a serine protease secreted by cells of myeloid lineage and allocated to the cell surface of neutrophils and endothelial cells.…”

Rapid qPCR-based quantitative immune cell phenotyping in mouse tissues

“…21,22,35 In addition to the cell types mentioned above, other immune cell types are also relevant for different diseases. 36–41…”

“…21,22,35 In addition to the cell types mentioned above, other immune cell types are also relevant for different diseases. [36][37][38][39][40][41] Of note, the described PCR analysis was developed to obtain a rapid overview of the general cellular composition of the immune microenvironment. The method was not designed to discriminate accurately between different functional states or activation profiles of the different immune cell populations.…”