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

Bilal Alaiyan, Nadia Ilyayev, Alexander Stojadinovic, Mina Izadjoo, Marina Roistacher, Vera Pavlov, Victoria Tzivin, David Halle, Honguang Pan, Barry Trink, Ali O. Gure, Aviram Nissan

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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.

Original languageEnglish (US)
Article number196
JournalBMC cancer
Volume13
DOIs
StatePublished - Apr 17 2013

Keywords

  • Adenoma
  • Biomarkers
  • Carcinoma
  • Colon cancer
  • Non-coding RNA

ASJC Scopus subject areas

  • Genetics
  • Oncology
  • Cancer Research

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    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. (2013). Differential expression of colon cancer associated transcript1 (CCAT1) along the colonic adenoma-carcinoma sequence. BMC cancer, 13, [196]. https://doi.org/10.1186/1471-2407-13-196