Weng Meilin, Yue Ying, Wu Dan, Zhou Changming, Guo Miaomiao, Sun Caihong, Liao Qingwu, Sun Minli, Zhou Di, Miao Changhong
Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Anesthesiology, Shanghai Cancer Center, Fudan University, Shanghai, China.
Front Oncol. 2022 Jul 14;12:940706. doi: 10.3389/fonc.2022.940706. eCollection 2022.
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.
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.
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).
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.
髓过氧化物酶（MPO）已被证明是多种炎症性疾病组织损伤中炎症的局部介质。鉴于其对结直肠癌（CRC）的影响存在争议，人们对研究这种酶在CRC中的作用越来越感兴趣。MPO活性与CRC进展的潜在机制需要进一步阐明。
使用TCGA分析评估MPO在CRC中的表达和功能。利用TCGA、TIMER和人类细胞图谱分析来分析MPO表达与CRC中中性粒细胞浸润之间的相关性。采用Spearman双变量相关性分析来验证CRC中MPO水平与外周血中性粒细胞计数之间的相关性。在临床分析中，2008年1月至2014年12月期间，8121例接受择期CRC手术的患者被纳入这项回顾性队列研究。采用倾向评分匹配法来解决基线特征的差异。使用Kaplan-Meier法和Cox回归分析来确定CRC患者的独立预后因素。
根据TCGA分析，MPO在CRC组织中上调，这与CRC患者的恶性进展和较差的生存率相关。在TCGA、TIMER和人类细胞图谱分析中，MPO与CRC中中性粒细胞的浸润水平显著相关。MPO与外周血中性粒细胞计数呈正相关。8121例接受CRC手术患者的数据可供分析。经过倾向评分匹配后，每组纳入3358例患者。Kaplan-Meier生存曲线显示，术前中性粒细胞水平高与总生存期（OS；P<0.001）和无病生存期（DFS；P=0.015）降低相关。术前中性粒细胞计数是OS（风险比[HR]，1.157；95%置信区间[CI]，1.055-1.268；P=0.002）和DFS（HR，1.118；95%CI，1.009-1.238；P=0.033）的独立危险因素。
我们的研究表明，CRC中MPO水平升高与术前中性粒细胞计数高显著相关，两者均为CRC患者较差生存率的预后指标。我们的研究表明，中性粒细胞可能是将MPO水平与CRC不良结局联系起来的机制中的关键因素。
