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

Oncotarget. 2017 Apr 11;8(15):24892-24901. doi: 10.18632/oncotarget.15279.

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.

Keywords: biomarker; colorectal cancer; liver metastasis; prognosis; screening.

MeSH terms

  • Biomarkers, Tumor / blood*
  • Carcinoembryonic Antigen / blood*
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / pathology
  • Female
  • Growth Differentiation Factor 15 / blood*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Prognosis
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • Carcinoembryonic Antigen
  • GDF15 protein, human
  • Growth Differentiation Factor 15