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      Differential expression of colon cancer associated transcript1 (CCAT1) along the colonic adenoma-carcinoma sequence

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      Author
      Alaiyan, B.
      Ilyayev, N.
      Stojadinovic, A.
      Izadjoo, M.
      Roistacher, M.
      Pavlov, V.
      Tzivin, V.
      Halle, D.
      Pan, H.
      Trink, B.
      Gure, A. O.
      Nissan, A.
      Date
      2013
      Source Title
      BMC Cancer
      Print ISSN
      1471-2407
      Publisher
      BioMed Central
      Volume
      13
      Language
      English
      Type
      Article
      Item Usage Stats
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      137
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      Abstract
      Background: The transition from normal epithelium to adenoma and, to invasive carcinoma in the human colon is associated with acquired molecular events taking 5-10 years for malignant transformation. We discovered CCAT1, a non-coding RNA over-expressed in colon cancer (CC), but not in normal tissues, thereby making it a potential disease-specific biomarker. We aimed to define and validate CCAT1 as a CC-specific biomarker, and to study CCAT1 expression across the adenoma-carcinoma sequence of CC tumorigenesis.Methods: Tissue samples were obtained from patients undergoing resection for colonic adenoma(s) or carcinoma. Normal colonic tissue (n = 10), adenomatous polyps (n = 18), primary tumor tissue (n = 22), normal mucosa adjacent to primary tumor (n = 16), and lymph node(s) (n = 20), liver (n = 8), and peritoneal metastases (n = 19) were studied. RNA was extracted from all tissue samples, and CCAT1 expression was analyzed using quantitative real time-PCR (qRT-PCR) with confirmatory in-situ hybridization (ISH).Results: Borderline expression of CCAT1 was identified in normal tissue obtained from patients with benign conditions [mean Relative Quantity (RQ) = 5.9]. Significant relative CCAT1 up-regulation was observed in adenomatous polyps (RQ = 178.6 ± 157.0; p = 0.0012); primary tumor tissue (RQ = 64.9 ± 56.9; p = 0.0048); normal mucosa adjacent to primary tumor (RQ = 17.7 ± 21.5; p = 0.09); lymph node, liver and peritoneal metastases (RQ = 11,414.5 ± 12,672.9; 119.2 ± 138.9; 816.3 ± 2,736.1; p = 0.0001, respectively). qRT-PCR results were confirmed by ISH, demonstrating significant correlation between CCAT1 up-regulation measured using these two methods.Conclusion: CCAT1 is up-regulated across the colon adenoma-carcinoma sequence. This up-regulation is evident in pre-malignant conditions and through all disease stages, including advanced metastatic disease suggesting a role in both tumorigenesis and the metastatic process. © 2013 Alaiyan et al.; licensee BioMed Central Ltd.
      Keywords
      Colon cancer
      Non-coding RNA
      Biomarkers
      Adenoma
      Carcinoma
      Permalink
      http://hdl.handle.net/11693/21005
      Published Version (Please cite this version)
      http://dx.doi.org/10.1186/1471-2407-13-196
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