title: Circulating MIC-1/GDF15 is a complementary screening biomarker with CEA and correlates with liver metastasis and poor survival in colorectal cancer.
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.
authors.affiliation: Tumor Marker Research Center, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Wang
authors.affiliation: NSF Nanoscale Science and Engineering Center (NSEC), The Ohio State University, Columbus, OH, USA.
authors.forename: Zhaogang
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Tumor Marker Research Center, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
authors.forename: Haimei
authors.initials: H
authors.lastname: Tian
authors.affiliation: Tumor Marker Research Center, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
authors.forename: Yanfen
authors.initials: Y
authors.lastname: Li
authors.affiliation: Tumor Marker Research Center, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
authors.forename: Mo
authors.initials: M
authors.lastname: Li
authors.affiliation: Tumor Marker Research Center, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
authors.forename: Wenya
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Tumor Marker Research Center, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Tumor Marker Research Center, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
authors.forename: Teng
authors.initials: T
authors.lastname: Wang
authors.affiliation: Tumor Marker Research Center, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: NSF Nanoscale Science and Engineering Center (NSEC), The Ohio State University, Columbus, OH, USA.
authors.forename: Aili
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Laboratory of Clinical Biochemistry, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
authors.forename: Di
authors.initials: D
authors.lastname: Shen
authors.affiliation: Laboratory of Clinical Biochemistry, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
authors.forename: Cuining
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Laboratory of Clinical Biochemistry, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of Gynecological Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.affiliation: NSF Nanoscale Science and Engineering Center (NSEC), The Ohio State University, Columbus, OH, USA.|Department of Mechanical Engineering, The Ohio State University, Columbus, OH, USA.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, LA, USA.
authors.forename: Liliang
authors.initials: L
authors.lastname: Jin
authors.affiliation: Tumor Marker Research Center, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
authors.forename: Jianyu
authors.initials: J
authors.lastname: Rao
authors.affiliation: Tumor Marker Research Center, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D002272:Carcinoembryonic Antigen / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood* / Q000473:pathology; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15
keywords: biomarker; colorectal cancer; liver metastasis; prognosis; screening