title: Induction of KIAA1199/CEMIP is associated with colon cancer phenotype and poor patient survival.
abstract: Genes induced in colon cancer provide novel candidate biomarkers of tumor phenotype and aggressiveness. We originally identified KIAA1199 (now officially called CEMIP) as a transcript highly induced in colon cancer: initially designating the transcript as Colon Cancer Secreted Protein 1. We molecularly characterized CEMIP expression both at the mRNA and protein level and found it is a secreted protein induced an average of 54-fold in colon cancer. Knockout of CEMIPreduced the ability of human colon cancer cells to form xenograft tumors in athymic mice. Tumors that did grow had increased deposition of hyaluronan, linking CEMIP participation in hyaluronan degradation to the modulation of tumor phenotype. We find CEMIP mRNA overexpression correlates with poorer patient survival. In stage III only (n = 31) or in combined stage II plus stage III colon cancer cases (n = 73), 5-year overall survival was significantly better (p = 0.004 and p = 0.0003, respectively) among patients with low CEMIP expressing tumors than those with high CEMIP expressing tumors. These results demonstrate that CEMIP directly facilitates colon tumor growth, and high CEMIP expression correlates with poor outcome in stage III and in stages II+III combined cohorts. We present CEMIP as a candidate prognostic marker for colon cancer and a potential therapeutic target.
authors.affiliation: Department of Medicine, Case Western Reserve University and Case Medical Center, Cleveland, OH, USA.|Case Comprehensive Cancer Center, Case Western Reserve University and Case Medical Center, Cleveland, OH, USA.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Fink
authors.affiliation: Department of Medicine, Case Western Reserve University and Case Medical Center, Cleveland, OH, USA.|Case Comprehensive Cancer Center, Case Western Reserve University and Case Medical Center, Cleveland, OH, USA.
authors.forename: Lois L
authors.initials: LL
authors.lastname: Myeroff
authors.affiliation: Department of Medicine, Case Western Reserve University and Case Medical Center, Cleveland, OH, USA.|Case Comprehensive Cancer Center, Case Western Reserve University and Case Medical Center, Cleveland, OH, USA.
authors.forename: Revital
authors.initials: R
authors.lastname: Kariv
authors.affiliation: Department of Medicine, Case Western Reserve University and Case Medical Center, Cleveland, OH, USA.|Case Comprehensive Cancer Center, Case Western Reserve University and Case Medical Center, Cleveland, OH, USA.|Genomic Medicine Institute, Lerner Research Institute Cleveland Clinic Foundation, Cleveland, OH, USA.
authors.forename: Petra
authors.initials: P
authors.lastname: Platzer
authors.affiliation: Department of Medicine, Case Western Reserve University and Case Medical Center, Cleveland, OH, USA.|Case Comprehensive Cancer Center, Case Western Reserve University and Case Medical Center, Cleveland, OH, USA.
authors.forename: Baozhong
authors.initials: B
authors.lastname: Xin
authors.affiliation: Department of Medicine, Case Western Reserve University and Case Medical Center, Cleveland, OH, USA.|Case Comprehensive Cancer Center, Case Western Reserve University and Case Medical Center, Cleveland, OH, USA.
authors.forename: Debra
authors.initials: D
authors.lastname: Mikkola
authors.affiliation: Department of Medicine, Case Western Reserve University and Case Medical Center, Cleveland, OH, USA.|Case Comprehensive Cancer Center, Case Western Reserve University and Case Medical Center, Cleveland, OH, USA.
authors.forename: Earl
authors.initials: E
authors.lastname: Lawrence
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University and Case Medical Center, Cleveland, OH, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Morris
authors.affiliation: Department of Medicine, Case Western Reserve University and Case Medical Center, Cleveland, OH, USA.|Case Comprehensive Cancer Center, Case Western Reserve University and Case Medical Center, Cleveland, OH, USA.
authors.forename: Arman
authors.initials: A
authors.lastname: Nosrati
authors.affiliation: Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: James K V
authors.initials: JK
authors.lastname: Willson
authors.affiliation: Department of Pathology, Case Western Reserve University and Case Medical Center, Cleveland, OH, USA.|Case Comprehensive Cancer Center, Case Western Reserve University and Case Medical Center, Cleveland, OH, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Willis
authors.affiliation: Department of Medicine, Case Western Reserve University and Case Medical Center, Cleveland, OH, USA.|Case Comprehensive Cancer Center, Case Western Reserve University and Case Medical Center, Cleveland, OH, USA.
authors.forename: Martina
authors.initials: M
authors.lastname: Veigl
authors.affiliation: Case Comprehensive Cancer Center, Case Western Reserve University and Case Medical Center, Cleveland, OH, USA.
authors.forename: Jill S
authors.initials: JS
authors.lastname: Barnholtz-Sloan
authors.affiliation: Department of Genetics and Genome Sciences, Case Western Reserve University and Case Medical Center, Cleveland, OH, USA.|Case Comprehensive Cancer Center, Case Western Reserve University and Case Medical Center, Cleveland, OH, USA.
authors.forename: Zhenghe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Medicine, Case Western Reserve University and Case Medical Center, Cleveland, OH, USA.|Case Comprehensive Cancer Center, Case Western Reserve University and Case Medical Center, Cleveland, OH, USA.
authors.forename: Sanford D
authors.initials: SD
authors.lastname: Markowitz
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D003106:Colon / Q000166:cytology / Q000378:metabolism; D003110:Colonic Neoplasms / Q000401:mortality* / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055786:Gene Knockout Techniques; D006367:HeLa Cells; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D006821:Hyaluronoglucosaminidase; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D014183:Transplantation, Heterologous
chemical_list: D014408:Biomarkers, Tumor; D011506:Proteins; D012333:RNA, Messenger; D006820:Hyaluronic Acid; C491433:CEMIP protein, human; D006821:Hyaluronoglucosaminidase
keywords: CEMIP; colon cancer; metastasis; prognostic marker; secreted protein