Department of Gastrointestinal Surgery, The first Affiliated Hospital of Bengbu Medical College, Bengbu, China.
Department of Cardiovascular Surgery, Tianjin First Central Hospital, Tianjin, China.
Cancer Med. 2018 Aug;7(8):3682-3694. doi: 10.1002/cam4.1663. Epub 2018 Jul 13.
Interleukin (IL)-37 and neutrophils are considered to be involved in human cancer, but their prognostic significance in colorectal cancer (CRC) has not been elucidated. The aim of this study was to evaluate the prognostic value of IL-37 expression and neutrophil levels in CRC. We retrospectively analyzed IL-37 expression, CD66b neutrophil levels, and mismatch repair (MMR) status in 337 paraffin-embedded CRC specimens from the training cohort by immunohistochemistry. Their prognostic values were assessed using Kaplan-Meier curves and multivariate Cox regression models. Moreover, several risk factors were used to form nomograms to evaluate survival, and the performance of the nomograms was assessed with respect to calibration, discrimination, and clinical usefulness. Further validation was performed in an independent cohort of 245 cases. Low IL-37 expression and high CD66b neutrophil levels were significantly associated with diminished disease-free survival (DFS) and overall survival (OS), and patients with MMR-deficient CRC had better clinical outcomes. Furthermore, multivariate Cox analysis identified IL-37, CD66b neutrophils, and MMR status as independent prognostic factors for DFS and OS. Two nomograms integrating the three markers with four clinicopathological risk factors were developed and validated for predicting DFS and OS with good calibration and discrimination (C-index: training cohort, 0.798 (95% confidence interval:0.764-0.832) and 0.828 (0.796-0.860), respectively; validation cohort, 0.739 (0.696-0.783) and 0.761 (0.715-0.808), respectively). Decision curve analysis demonstrated that the nomograms were clinically useful. Intratumoral IL-37, CD66b neutrophils, and MMR status were independent prognostic factors for CRC patients. Nomograms incorporating these biomarkers and clinicopathological features could be conveniently used to facilitate the individualized prediction of DFS and OS.
白细胞介素 (IL)-37 和中性粒细胞被认为与人类癌症有关，但它们在结直肠癌 (CRC) 中的预后意义尚未阐明。本研究旨在评估 IL-37 表达和中性粒细胞水平在 CRC 中的预后价值。我们通过免疫组织化学分析，对来自训练队列的 337 例石蜡包埋 CRC 标本中的 IL-37 表达、CD66b 中性粒细胞水平和错配修复 (MMR) 状态进行了回顾性分析。我们使用 Kaplan-Meier 曲线和多变量 Cox 回归模型评估了它们的预后价值。此外，我们使用几个风险因素来构建列线图以评估生存，并且评估了列线图的校准、区分度和临床实用性。在 245 例独立队列中进行了进一步验证。低 IL-37 表达和高 CD66b 中性粒细胞水平与疾病无进展生存期 (DFS) 和总生存期 (OS) 降低显著相关，并且 MMR 缺陷型 CRC 患者具有更好的临床结局。此外，多变量 Cox 分析确定 IL-37、CD66b 中性粒细胞和 MMR 状态是 DFS 和 OS 的独立预后因素。两个整合了三个标志物和四个临床病理危险因素的列线图被开发并验证用于预测 DFS 和 OS，具有良好的校准和区分度（C 指数：训练队列分别为 0.798（95%置信区间：0.764-0.832）和 0.828（0.796-0.860）；验证队列分别为 0.739（0.696-0.783）和 0.761（0.715-0.808））。决策曲线分析表明，这些列线图具有临床实用性。肿瘤内 IL-37、CD66b 中性粒细胞和 MMR 状态是 CRC 患者的独立预后因素。纳入这些生物标志物和临床病理特征的列线图可方便地用于促进 DFS 和 OS 的个体化预测。
