Open Access Research article

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

Bilal Alaiyan1, Nadia Ilyayev1, Alexander Stojadinovic23, Mina Izadjoo2, Marina Roistacher1, Vera Pavlov1, Victoria Tzivin1, David Halle1, Honguang Pan2, Barry Trink4, Ali O Gure5 and Aviram Nissan16*

Author Affiliations

1 The Surgical Oncology Laboratory, Department of Surgery, Hadassah-Hebrew University Medical Center, Mount Scopus, POB 12000, Jerusalem, 91120, Israel

2 Diagnostics and Translational Research Center Henry M Jackson Foundation for the Advancement of Military Medicine, Gaithersburg, MD, 20879, USA

3 The Department of Surgery, Division of Surgical Oncology, Walter Reed National Medical Center, Bethesda, MD, USA

4 Johns Hopkins School of Medicine, Baltimore, MA, USA

5 Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey

6 Department of Surgery, Hadassah-Hebrew University Medical Center Ein Kerem, Jerusalem, Israel

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BMC Cancer 2013, 13:196  doi:10.1186/1471-2407-13-196

Published: 17 April 2013

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.

Keywords:
Colon cancer; Non-coding RNA; Biomarkers; Adenoma; Carcinoma