title: Macrophage inhibitory cytokine 1 (MIC-1/GDF15) as a novel diagnostic serum biomarker in pancreatic ductal adenocarcinoma.
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.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Wang
authors.forename: Yanfen
authors.initials: Y
authors.lastname: Li
authors.forename: Haimei
authors.initials: H
authors.lastname: Tian
authors.forename: Jun
authors.initials: J
authors.lastname: Qi
authors.forename: Mo
authors.initials: M
authors.lastname: Li
authors.forename: Chao
authors.initials: C
authors.lastname: Fu
authors.forename: Fan
authors.initials: F
authors.lastname: Wu
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Dongwan
authors.initials: D
authors.lastname: Cheng
authors.forename: Wenya
authors.initials: W
authors.lastname: Zhao
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Teng
authors.initials: T
authors.lastname: Wang
authors.forename: Jianyu
authors.initials: J
authors.lastname: Rao
authors.affiliation: Medical Center for Tumor Detection, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, PR China. zhangww1954@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D018395:CA-19-9 Antigen / Q000097:blood; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood* / Q000175:diagnosis / Q000601:surgery; D016022:Case-Control Studies; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15
references.citation: J Biol Chem. 1998 May 29;273(22):13760-7
references.pmid: 9593718
references.citation: Crit Rev Oncol Hematol. 2006 Jun;58(3):231-41
references.pmid: 16725343
references.citation: Pancreatology. 2011;11(3):295-300
references.pmid: 21757969
references.citation: J Gastrointest Surg. 2006 Nov;10(9):1212-23; discussion 1223-4
references.pmid: 17114008
references.citation: Ann Surg. 1996 Mar;223(3):273-9
references.pmid: 8604907
references.citation: Clin Cancer Res. 2006 Jan 1;12(1):89-96
references.pmid: 16397029
references.citation: J Invest Dermatol. 2009 Feb;129(2):383-91
references.pmid: 18754039
references.citation: Gynecol Oncol. 2010 Sep;118(3):237-43
references.pmid: 20576287
references.citation: Cancer Res. 2003 Aug 15;63(16):5034-40
references.pmid: 12941831
references.citation: Cancer Sci. 2014 Feb;105(2):176-85
references.pmid: 24383865
references.citation: Cancer Epidemiol Biomarkers Prev. 2012 Feb;21(2):337-46
references.pmid: 22144502
references.citation: Clin Cancer Res. 2006 Jan 15;12(2):442-6
references.pmid: 16428484
references.citation: Clin Cancer Res. 2011 Feb 15;17(4):805-16
references.pmid: 21325298
references.citation: Eur J Surg Oncol. 2007 Apr;33(3):266-70
references.pmid: 17097848
references.citation: J Clin Oncol. 2006 Nov 20;24(33):5313-27
references.pmid: 17060676
references.citation: Am J Pathol. 2010 Jun;176(6):2948-57
references.pmid: 20431030
references.citation: Growth Factors. 2011 Oct;29(5):187-95
references.pmid: 21831009
references.citation: Oncogene. 2010 Mar 4;29(9):1293-302
references.pmid: 19946339
references.citation: Oncology. 1995 Jan-Feb;52(1):19-23
references.pmid: 7800337
references.citation: Clin Cancer Res. 2004 Apr 1;10(7):2386-92
references.pmid: 15073115
references.citation: Clin Cancer Res. 2003 Jul;9(7):2642-50
references.pmid: 12855642
references.citation: CA Cancer J Clin. 2012 Jan-Feb;62(1):10-29
references.pmid: 22237781
references.citation: J Biol Chem. 2000 Jun 30;275(26):20127-35
references.pmid: 10777512
references.citation: Cancer Res. 2003 Aug 1;63(15):4648-55
references.pmid: 12907645
references.citation: Br J Cancer. 2010 Feb 16;102(4):665-72
references.pmid: 20104227
references.citation: Int J Surg. 2013;11(10):1067-72
references.pmid: 24161419
references.citation: Biochem Pharmacol. 2009 Nov 1;78(9):1205-13
references.pmid: 19540205
references.citation: Cancer Res. 2006 May 15;66(10):4983-6
references.pmid: 16707416
references.citation: J Natl Cancer Inst. 2014 Apr;106(4):dju016
references.pmid: 24565956
references.citation: Cancer Res. 2001 Oct 1;61(19):6996-7001
references.pmid: 11585723
references.citation: Mol Carcinog. 2009 Aug;48(8):692-702
references.pmid: 19125423
references.citation: Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11514-9
references.pmid: 9326641
references.citation: PLoS One. 2013;8(2):e55171
references.pmid: 23383312
references.citation: Carcinogenesis. 2008 Apr;29(4):704-12
references.pmid: 18258606
references.citation: Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3410-5
references.pmid: 12624183
references.citation: Eur J Surg Oncol. 2005 Mar;31(2):164-9
references.pmid: 15698733
references.citation: Lancet. 2004 Mar 27;363(9414):1049-57
references.pmid: 15051286
references.citation: J Cell Physiol. 2010 Sep;224(3):626-35
references.pmid: 20578239
references.citation: Aging Cell. 2010 Dec;9(6):1057-64
references.pmid: 20854422
references.citation: Cancer Epidemiol Biomarkers Prev. 2007 Mar;16(3):532-7
references.pmid: 17372249
references.citation: Mol Cell Biol. 2000 May;20(10):3742-51
references.pmid: 10779363