Macrophage Inhibitory Cytokine 1 (MIC-1/GDF15) as a Novel Diagnostic Serum Biomarker in Pancreatic Ductal Adenocarcinoma

BMC Cancer. 2014 Aug 8;14:578. doi: 10.1186/1471-2407-14-578.

Abstract

Background: Macrophage inhibitory cytokine 1 (MIC-1/GDF15) has been identified as a potential novel biomarker for detection of pancreatic cancer (PCa). However, the diagnostic value of serum MIC-1 for pancreatic ductal adenocarcinoma (PDAC), particularly for those at the early stage, and the value for treatment response monitoring have not yet been investigated.

Methods: MIC-1 expression in tumor tissue was analyzed by RT-PCR from 64 patients with PDAC. Serum MIC-1 levels were detected by ELISA in 1472 participants including PDAC, benign pancreas tumor, chronic pancreatitis and normal controls. The diagnostic performance of MIC-1 was assessed and compared with CA19.9, CEA and CA242, and the value of it as a predictive indicator for therapeutic response and tumor recurrence was also evaluated.

Results: MIC-1 levels were significantly elevated in PDAC tissues as well as serum samples. The sensitivity of serum MIC-1 for PDAC diagnosis was much higher than that of CA19.9 (65.8% vs. 53.3%) with similar specificities. Furthermore, serum MIC-1 detected 238 out of 377 (63.1%) CA19.9-negative PDAC. Moreover, receiver operating characteristic (ROC) curve analysis also showed that serum MIC-1 had a better performance compared with CA19.9 in distinguishing early-stage PDAC from normal serum with a higher sensitivity (62.5% vs. 25.0% respectively). Notably, serum MIC-1 level was significantly decreased in patients with PDAC after curative resection and returned to elevated levels when tumor relapse occurred.

Conclusions: Serum MIC-1 is significantly elevated in most PDAC, including those with negative CA19.9 and early stage disease, and thus may serve as a novel diagnostic marker in early diagnosis and postoperative monitoring of PDAC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • CA-19-9 Antigen / blood
  • Carcinoma, Pancreatic Ductal / blood*
  • Carcinoma, Pancreatic Ductal / diagnosis
  • Carcinoma, Pancreatic Ductal / surgery
  • Case-Control Studies
  • Female
  • Growth Differentiation Factor 15 / blood
  • Growth Differentiation Factor 15 / genetics*
  • Humans
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / blood*
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • CA-19-9 Antigen
  • GDF15 protein, human
  • Growth Differentiation Factor 15