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

Meilin Weng; Ying Yue; Dan Wu; Changming Zhou; Miaomiao Guo; Caihong Sun; Qingwu Liao; Minli Sun; Di Zhou; Changhong Miao

doi:10.3389/fonc.2022.940706

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

Front Oncol. 2022 Jul 14:12:940706. doi: 10.3389/fonc.2022.940706. eCollection 2022.

Authors

Meilin Weng^{1

2

3}, Ying Yue^{1

3}, Dan Wu^{1

3}, Changming Zhou⁴, Miaomiao Guo^{1

3}, Caihong Sun^{1

3}, Qingwu Liao^{1

3}, Minli Sun^{1

3}, Di Zhou^{1

3}, Changhong Miao^{1

3}

Affiliations

¹ Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China.
² Department of Anesthesiology, Shanghai Cancer Center, Fudan University, Shanghai, China.
³ Shanghai Key Laboratory of Perioperative Stress and Protection, Zhongshan Hospital, Fudan University, Shanghai, China.
⁴ Department of Cancer Prevention, Shanghai Cancer Center, Fudan University, Shanghai, China.

Abstract

Background: Myeloperoxidase (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.

Methods: The 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.

Results: MPO 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).

Conclusions: Our 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.

Keywords: TCGA analysis; colorectal cancer; myeloperoxidase; preoperative neutrophil counts; prognosis; propensity score-matched analysis.