Circulating MIC-1/GDF15 is a complementary screening biomarker with CEA and correlates with liver metastasis and poor survival in colorectal cancer

// Xiaobing Wang 1, * , Zhaogang Yang 2, * , Haimei Tian 1 , Yanfen Li 1 , Mo Li 1 , Wenya Zhao 1 , Chao Zhang 1 , Teng Wang 1 , Jing Liu 1 , Aili Zhang 2 , Di Shen 3 , Cuining Zheng 3 , Jun Qi 3 , Dan Zhao 4 , Junfeng Shi 2, 5 , Liliang Jin 6 , Jianyu Rao 1 , Wei Zhang 1 1 Tumor Marker Research Center, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China 2 NSF Nanoscale Science and Engineering Center (NSEC), The Ohio State University, Columbus, OH, USA 3 Laboratory of Clinical Biochemistry, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China 4 Department of Gynecological Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China 5 Department of Mechanical Engineering, The Ohio State University, Columbus, OH, USA 6 Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, LA, USA * These authors have contributed equally to this work Correspondence to: Wei Zhang, email: zhangww1954@126.com Keywords: colorectal cancer, biomarker, screening, liver metastasis, prognosis Received: September 13, 2016     Accepted: January 06, 2017     Published: February 11, 2017 ABSTRACT 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.