Zhang Yiyin, Hu Yangyang, Ma Cui, Sun Hua, Wei Xiaoli, Li Min, Wei Wei, Zhang Fei, Yang Feng, Wang Hua, Gu Kangsheng
Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Department of Pathology, Basic Medical School of Anhui Medical University, Hefei, China.
Front Oncol. 2020 Jun 26;10:1036. doi: 10.3389/fonc.2020.01036. eCollection 2020.
Neutrophils are a significant population of infiltrated immune cells in the tumor microenvironment. Neutrophil extracellular traps (NETs) are implicated in the biological behavior of many malignant tumors. NETs can be degraded into soluble nucleosomes, leading to the release of fragments containing DNA and granule proteins into the peripheral blood (PB). Using human gastric cancer (GC) biopsies and PB samples, we investigated the specific value of NETs in GC from a clinical perspective. In summary, the formation of NETs was discovered in the tissue microenvironment and PB of GC patients. The amounts of NETs and neutrophil accumulation decreased from tumor tissue to paratumor tissue. In addition, the level of NETs in the PB gradually declined through the following patient populations: advanced disease patients, preoperative patients, postoperative patients, benign disease patients, and healthy controls. The levels of NETs in the plasma and serum were significantly correlated. As a serum biomarker, NETs had a better diagnostic value than carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in GC. The neutrophil count and neutrophil to lymphocyte ratio (NLR) were significantly associated with the level of NETs in the PB. The existence of lymph node metastasis indicated a high level of NETs in the serum. Moreover, the level of NETs in the PB was inversely correlated with short-term efficacy in GC patients who had received advanced first-line treatment. The higher baseline level of NETs in the PB of patients with negative HER2 status was correlated with worse progression-free survival (PFS). And the level of NETs in the PB was a unfavorable independent prognostic factor for PFS in patients with advanced GC who had received first-line treatment. Thus, NETs have novel diagnostic, therapeutic predictive, and prognostic value in GC patients.
中性粒细胞是肿瘤微环境中浸润的免疫细胞的重要组成部分。中性粒细胞胞外陷阱（NETs）与许多恶性肿瘤的生物学行为有关。NETs可降解为可溶性核小体，导致含有DNA和颗粒蛋白的片段释放到外周血（PB）中。我们使用人胃癌（GC）活检组织和PB样本，从临床角度研究了NETs在GC中的具体价值。总之，在GC患者的组织微环境和PB中发现了NETs的形成。NETs的数量和中性粒细胞的积聚从肿瘤组织到瘤旁组织逐渐减少。此外，PB中NETs的水平在以下患者群体中逐渐下降：晚期疾病患者、术前患者、术后患者、良性疾病患者和健康对照。血浆和血清中NETs的水平显著相关。作为一种血清生物标志物，NETs在GC中的诊断价值优于癌胚抗原（CEA）和糖类抗原19-9（CA19-9）。中性粒细胞计数和中性粒细胞与淋巴细胞比值（NLR）与PB中NETs的水平显著相关。淋巴结转移的存在表明血清中NETs水平较高。此外，PB中NETs的水平与接受晚期一线治疗的GC患者的短期疗效呈负相关。HER2状态阴性的患者PB中NETs的基线水平越高，无进展生存期（PFS）越差。并且PB中NETs的水平是接受一线治疗的晚期GC患者PFS的不良独立预后因素。因此，NETs在GC患者中具有新的诊断、治疗预测和预后价值。
