Oncotarget

Priority Research Papers:

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 and Sanford D. Markowitz _

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Oncotarget. 2015; 6:30500-30515. https://doi.org/10.18632/oncotarget.5921

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Abstract

Stephen P. Fink1,5, Lois L. Myeroff1,5, Revital Kariv1,5, Petra Platzer1,5,7, Baozhong Xin1,5, Debra Mikkola1,5, Earl Lawrence1,5, Nathan Morris3, Arman Nosrati1,5, James K. V. Willson6, Joseph Willis2,5, Martina Veigl1,5, Jill S. Barnholtz-Sloan5, Zhenghe Wang4,5 and Sanford D. Markowitz1,5

1 Department of Medicine, Case Western Reserve University, and Case Medical Center, Cleveland, OH, USA

2 Department of Pathology, Case Western Reserve University, and Case Medical Center, Cleveland, OH, USA

3 Department of Epidemiology and Biostatistics, Case Western Reserve University, and Case Medical Center, Cleveland, OH, USA

4 Department of Genetics and Genome Sciences, Case Western Reserve University, and Case Medical Center, Cleveland, OH, USA

5 Case Comprehensive Cancer Center, Case Western Reserve University, and Case Medical Center, Cleveland, OH, USA

6 Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA

7 Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA

Correspondence to:

Sanford D. Markowitz, email:

Stephen P. Fink, email:

Keywords: colon cancer, CEMIP, secreted protein, prognostic marker, metastasis

Received: July 28, 2015 Accepted: September 08, 2015 Published: September 30, 2015

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.


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