Wang Xiaobing, Yang Zhaogang, Tian Haimei, Li Yanfen, Li Mo, Zhao Wenya, Zhang Chao, Wang Teng, Liu Jing, Zhang Aili, Shen Di, Zheng Cuining, Qi Jun, Zhao Dan, Shi Junfeng, Jin Liliang, Rao Jianyu, Zhang Wei
Tumor Marker Research Center, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
NSF Nanoscale Science and Engineering Center (NSEC), The Ohio State University, Columbus, OH, USA.
Oncotarget. 2017 Apr 11;8(15):24892-24901. doi: 10.18632/oncotarget.15279.
Macrophage inhibitory cytokine 1 (MIC-1/GDF15) has been characterized as a candidate biomarker for colorectal cancer (CRC) recently. However, the role of serum MIC-1 in screening patients with early stage CRC and monitoring therapeutic response have not been well-established, particularly in the combination with CEA for the screening and the prejudgment of occurrence with liver metastasis. In this study, we performed a retrospective blinded evaluation of 987 serum samples from 473 individuals with CRC, 25 with adenomatous polyps, and 489 healthy individuals using ELISA or immunoassay. The sensitivity of serum MIC-1 was 43.8% and 38.5% for CRC diagnosis and early diagnosis, respectively, which were independent of and comparatively higher than for CEA (36.6% and 27.3%) at comparable specificity. Serum MIC-1 after surgery were significantly elevated at the time of tumor recurrence, and notable increase were observed in 100% patients with liver metastasis. Besides the TNM classification and differentiation grade, MIC-1 was an independent prognostic factor contributing to overall survival. We conclude that MIC-1 can act as a candidate complementary biomarker for screening early-stage CRC by combination with CEA, and furthermore, for the first time, identify a promising prognostic indicator for monitoring recurrence with liver metastasis, to support strategies towards personalized therapy.
巨噬细胞抑制细胞因子1（MIC-1/GDF15）最近已被确定为结直肠癌（CRC）的候选生物标志物。然而，血清MIC-1在早期CRC患者筛查及监测治疗反应中的作用尚未完全明确，尤其是与癌胚抗原（CEA）联合用于筛查及预判肝转移发生情况时。在本研究中，我们采用酶联免疫吸附测定（ELISA）或免疫测定法，对473例CRC患者、25例腺瘤性息肉患者及489例健康个体的987份血清样本进行了回顾性盲法评估。血清MIC-1对CRC诊断及早期诊断的敏感性分别为43.8%和38.5%，在特异性相当的情况下，其与CEA（36.6%和27.3%）无关且相对更高。术后血清MIC-1在肿瘤复发时显著升高，100%肝转移患者出现明显升高。除了TNM分期和分化程度外，MIC-1是影响总生存期的独立预后因素。我们得出结论，MIC-1可作为与CEA联合筛查早期CRC的候选补充生物标志物，此外，首次确定了一个有前景的预后指标，用于监测肝转移复发情况，以支持个性化治疗策略。
