Colon cancer associated transcript-1: a novel RNA expressed in malignant and pre-malignant human tissues

Int J Cancer. 2012 Apr 1;130(7):1598-606. doi: 10.1002/ijc.26170. Epub 2011 Aug 2.

Abstract

Early detection of colorectal cancer (CRC) is currently based on fecal occult blood testing (FOBT) and colonoscopy, both which can significantly reduce CRC-related mortality. However, FOBT has low-sensitivity and specificity, whereas colonoscopy is labor- and cost-intensive. Therefore, the discovery of novel biomarkers that can be used for improved CRC screening, diagnosis, staging and as targets for novel therapies is of utmost importance. To identify novel CRC biomarkers we utilized representational difference analysis (RDA) and characterized a colon cancer associated transcript (CCAT1), demonstrating consistently strong expression in adenocarcinoma of the colon, while being largely undetectable in normal human tissues (p < 000.1). CCAT1 levels in CRC are on average 235-fold higher than those found in normal mucosa. Importantly, CCAT1 is strongly expressed in tissues representing the early phase of tumorigenesis: in adenomatous polyps and in tumor-proximal colonic epithelium, as well as in later stages of the disease (liver metastasis, for example). In CRC-associated lymph nodes, CCAT1 overexpression is detectable in all H&E positive, and 40.0% of H&E and immunohistochemistry negative lymph nodes, suggesting very high sensitivity. CCAT1 is also overexpressed in 40.0% of peripheral blood samples of patients with CRC but not in healthy controls. CCAT1 is therefore a highly specific and readily detectable marker for CRC and tumor-associated tissues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / genetics
  • Adenomatous Polyps / diagnosis
  • Adenomatous Polyps / genetics
  • Adolescent
  • Amino Acid Sequence
  • Base Sequence
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / pathology
  • Colonic Neoplasms / diagnosis
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • Early Detection of Cancer / methods
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Intestinal Mucosa / metabolism
  • Lymph Nodes / metabolism
  • Molecular Sequence Data
  • Mucous Membrane / metabolism
  • Neoplasm Metastasis
  • RNA Precursors / analysis
  • RNA Precursors / genetics*
  • RNA, Neoplasm / biosynthesis*
  • RNA, Neoplasm / genetics
  • Sensitivity and Specificity
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • RNA Precursors
  • RNA, Neoplasm