A prognostic classifier consisting of 17 circulating cytokines is a novel predictor of overall survival for metastatic colorectal cancer patients
A prognostic classifier consisting of 17 circulating cytokines is a novel predictor of overall survival for metastatic colorectal cancer patients
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由 17 种循环细胞因子组成的预后分类器是转移性结直肠癌患者总生存期的新预测因子
DOI：
10.1002/ijc.29017
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发表时间：
2015-02-15
影响因子：
6.4
通讯作者：
Qian, Chao-Nan
中科院分区：
文献类型：
--
作者：
Chen, Zhi-Yuan;He, Wen-Zhuo;Qian, Chao-Nan
我们的目的是确定中国转移性结直肠癌（CRC）患者中39种循环细胞因子的预后价值，并开发一种新的基于酪氨酸的预后分类器（CBPC）进行预后预测。共176例患者根据一线化疗日期分为两个队列。前99例病例被分配到培训队列，其余77例病例被分配到验证队列。使用基于多重珠的Luminex技术同时分析患者血清样品中的39种细胞因子。我们使用基于支持向量机的方法和考克斯比例风险模型从训练队列中开发CBPC，然后使用第二个患者队列进行验证。单因素分析显示FGF-2、TGF、Flt-3L、GM-CSF、INF-2、GRO、IL-10、MCP-3、MDC、sIL-2 R、IL-2、IL-7、IL-8、MCP-1、MIP-1、TNF和VEGF是影响训练队列和验证队列总生存期（OS）的显著危险因素。我们开发了一种CBPC，使用这17种细胞因子预测转移性CRC患者的OS（敏感性，0.835;特异性，0.800）。在验证队列中，发现CBPC在预测转移性CRC患者的OS方面具有显著的功效。我们的研究表明，细胞因子的表达与转移性结直肠癌患者的预后有显着的相关性。我们开发的CBPC包括多种循环细胞因子，可以作为一种新的筛选工具，用于识别具有高风险短OS的转移性CRC患者。这些高风险个体也可能适用于尼古丁靶向治疗。细胞因子及其受体是肿瘤微环境的重要调节因子。在结直肠癌中，某些细胞因子似乎与预后不良有关。本研究使用转移性疾病患者的样本评估了39种循环细胞因子在结直肠癌中的预后潜力。研究发现17种细胞因子是总生存期（OS）的重要危险因素。基于17种细胞因子的预后分类器可能是一种有价值的筛选工具，用于识别OS短的高风险患者和可能受益于靶向治疗的患者。
We aimed to determine the prognostic values of 39 circulating cytokines in Chinese patients with metastatic colorectal cancer (CRC) and to develop a novel cytokine-based prognostic classifier (CBPC) for prognostic prediction. A total of 176 patients were divided into two cohorts based on the date of first-line chemotherapy. The first 99 cases were assigned to the training cohort, and the remaining 77 cases were assigned to the validation cohort. Thirty-nine cytokines were simultaneously analyzed in the patient serum samples using multiplex bead-based Luminex technology. We used support vector machine-based methods and Cox proportional hazards models to develop a CBPC from the training cohort, which we then validated using the second patient cohort. Univariate analysis showed that FGF-2, TGF, Flt-3L, GM-CSF, INF2, GRO, IL-10, MCP-3, MDC, sIL-2R, IL-2, IL-7, IL-8, MCP-1, MIP-1, TNF and VEGF were significant risk factors affecting the overall survival (OS) of both the training cohort and the validation cohort. We developed a CBPC to predict the OS of metastatic CRC patients using these 17 cytokines (sensitivity, 0.835; specificity, 0.800). In the validation cohort, the CBPC was found to have significant power in predicting the OS of metastatic CRC patients. Our study showed that there were significant associations between cytokine expression and prognosis of the patients with metastatic CRC. The CBPC that we developed includes multiple circulating cytokines and may serve as a novel screening tool for identifying metastatic CRC patients with a high risk of short OS. These high-risk individuals may also be suitable for cytokine-targeted therapies.What's new? Cytokines and their receptors are important regulators of the tumor microenvironment. In colorectal cancer, certain cytokines appear to be linked to poor prognosis. This study assessed the prognostic potential in colorectal cancer of 39 circulating cytokines, using samples from patients with metastatic disease. Seventeen of the cytokines studied were found to be significant risk factors for overall survival (OS). A prognostic classifier based on the 17 cytokines could be a valuable screening tool for the identification of patients who are at high risk of short OS and who may benefit from cytokine-targeted therapies.