Tumor-Infiltrating NETs Predict Postsurgical Survival in Patients with Pancreatic Ductal Adenocarcinoma
Tumor-Infiltrating NETs Predict Postsurgical Survival in Patients with Pancreatic Ductal Adenocarcinoma
复制标题
肿瘤浸润性 NET 可预测胰腺导管腺癌患者的术后生存率。
DOI：
10.1245/s10434-018-6941-4
复制
发表时间：
2019-02-01
影响因子：
3.7
通讯作者：
Yu, Xian-Jun
中科院分区：
文献类型：
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作者：
Jin, Wei;Xu, Hua-Xiang;Yu, Xian-Jun
肿瘤浸润性中性粒细胞（TINs）提示胰腺导管腺癌（PDAC）患者预后不良。活化的中性粒细胞可以产生中性粒细胞胞外陷阱（NETs）。关于肿瘤浸润性NETs在PDAC中的存在及其预后意义知之甚少。本研究纳入了317例患者，分为两组（训练组和验证组），这些患者在上海癌症中心接受了根治性胰腺切除术。CD15和瓜氨酸组蛋白H3免疫组化染色分别鉴定tin和NETs。分析临床病理特征与预后的关系。采用一致性指数（C-index）和赤池信息准则（AIC）评价预后预测模型的准确性。NETs与训练集和验证集的OS（均P < 0.001）和RFS（均P < 0.001）相关。肿瘤浸润性NETs预测PDAC患者术后生存不良。此外，多变量分析发现NETs和AJCC TNM分期是OS和RFS的两个独立预后因素。net与第8版TNM分期系统（C-index分别为0.6994和0.6669；AIC分别为1067和1126）的结合产生了一个新的模型，提高了两组患者的生存预测准确性（C-index分别为0.7254和0.7117；AIC分别为1047和1102）。该模型将net与第七版AJCC TNM分期系统相结合，也提高了预测准确性。NETs是PDAC的一个独立预后因素，net与标准TNM状态系统的结合改善了PDAC的风险分层，并提高了预测生存率的准确性。
Tumor-infiltrating neutrophils (TINs) indicate poor prognosis for patients with pancreatic ductal adenocarcinoma (PDAC). Activated neutrophils can generate neutrophil extracellular traps (NETs). Little is known about the presence and prognostic significance of tumor-infiltrating NETs in PDAC.This study enrolled 317 patients, in two independent sets (training and validation), who underwent curative pancreatectomy for PDAC in Shanghai Cancer Center. TINs and NETs were identified by immunohistochemical staining for CD15 and citrullinated histone H3, respectively. The relationship between clinicopathological features and outcomes was analyzed. Accuracy of prognostic prediction models was evaluated using concordance index (C-index) and Akaike information criterion (AIC).NETs were associated with OS (both, P < 0.001) and RFS (both, P < 0.001) in the training and validation sets. Tumor-infiltrating NETs predicted poor postsurgical survival of patients with PDAC. Moreover, multivariate analysis identified NETs and AJCC TNM stage as two independent prognostic factors for OS and RFS. Combination of NETs with the 8th edition TNM staging system (C-index, 0.6994 and 0.6669, respectively; AIC, 1067 and 1126, respectively) generated a novel model that improved the predictive accuracy for survival in both sets (C-index, 0.7254 and 0.7117, respectively; AIC, 1047 and 1102, respectively). The model combining presence of NETs with the 7th edition AJCC TNM staging system also had improved predictive accuracy.NETs were an independent prognostic factor in PDAC and incorporation of NETs along with the standard TNM stating system refined risk-stratification and predicted survival in PDAC with improved accuracy.