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.
Highlights
Colon cancer is the second leading cause of cancer death among adult Americans, with an estimated 136,800 new cases and 50,300 deaths in 2014 [1]
We deposited the sequences encoding these transcripts in 2004 as GenBank accession numbers AY581148, AY585237, and AY581149, under the name Colon Cancer Secreted Protein 1 (CCSP1) before the gene name was officially changed to CEMIP
We have comprehensively characterized CEMIP expression in colon cancer and have provided the novel findings that CEMIP overexpression is associated with poor patient prognosis and is necessary for tumor growth
Summary
Colon cancer is the second leading cause of cancer death among adult Americans, with an estimated 136,800 new cases and 50,300 deaths in 2014 [1]. Patients with localized, resectable disease have a favorable prognosis with a 91% 5-year overall survival rate, yet survival rates decline significantly with disease progression [2]. Despite improved understanding www.impactjournals.com/oncotarget of the molecular events leading to colon cancer, there is a continued need for prognostic markers that can predict disease progression, metastasis, or recurrence in patients with the disease. Patients with stage II colon cancer, in which overall survival is already ~80% with surgery alone, the benefit of adjuvant therapy does not improve survival by more than 5%, underscoring the need for better prognostic markers to determine low from high risk stage II patients [4]. Elucidation of genes necessary for the metastatic process can lead to new avenues for targeted therapies
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