Chen Zhi-Yuan, He Wen-Zhuo, Peng Li-Xia, Jia Wei-Hua, Guo Rong-Ping, Xia Liang-Ping, Qian Chao-Nan
State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guang-zhou, People's Republic of China; Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
Int J Cancer. 2015 Feb 1;136(3):584-92. doi: 10.1002/ijc.29017. Epub 2014 Jun 24.
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, TGFα, Flt-3L, GM-CSF, INFα2, GRO, IL-10, MCP-3, MDC, sIL-2Rα, IL-2, IL-7, IL-8, MCP-1, MIP-1β, TNFα 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.
我们旨在确定39种循环细胞因子对中国转移性结直肠癌(CRC)患者的预后价值,并开发一种基于细胞因子的新型预后分类器(CBPC)用于预后预测。根据一线化疗日期,将176例患者分为两个队列。前99例被分配到训练队列,其余77例被分配到验证队列。使用基于多重微珠的Luminex技术同时分析患者血清样本中的39种细胞因子。我们使用基于支持向量机的方法和Cox比例风险模型从训练队列中开发出一种CBPC,然后使用第二个患者队列进行验证。单因素分析表明,FGF-2、TGFα、Flt-3L、GM-CSF、INFα2、GRO、IL-10、MCP-3、MDC、sIL-2Rα、IL-2、IL-7、IL-8、MCP-1、MIP-1β、TNFα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。我们使用这17种细胞因子开发了一种CBPC来预测转移性CRC患者的OS(敏感性为0.835;特异性为0.800)。在验证队列中,发现CBPC在预测转移性CRC患者的OS方面具有显著效力。我们的研究表明,细胞因子表达与转移性CRC患者的预后之间存在显著关联。我们开发的CBPC包含多种循环细胞因子,可作为一种新型筛查工具,用于识别总生存期短风险高的转移性CRC患者。这些高危个体也可能适合细胞因子靶向治疗。