Induction of KIAA1199/CEMIP is associated with colon cancer phenotype and poor patient survival

Stephen P. Fink, Lois L. Myeroff, Revital Kariv, Petra Platzer, Baozhong Xin, Debra Mikkola, Earl Lawrence, Nathan Morris, Arman Nosrati, James K V Willson, Joseph Willis, Martina Veigl, Jill S. Barnholtz-Sloan, Zhenghe Wang, Sanford D. Markowitz

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

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 CEMIP reduced 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.

Original languageEnglish (US)
Pages (from-to)30500-30515
Number of pages16
JournalOncotarget
Volume6
Issue number31
DOIs
StatePublished - 2015

Keywords

  • CEMIP
  • Colon cancer
  • Metastasis
  • Prognostic marker
  • Secreted protein

ASJC Scopus subject areas

  • Oncology

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