title: Differential expression of colon cancer associated transcript1 (CCAT1) along the colonic adenoma-carcinoma sequence.
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.
  
  
  CONCLUSIONS
  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.
authors.forename: Bilal
authors.initials: B
authors.lastname: Alaiyan
authors.forename: Nadia
authors.initials: N
authors.lastname: Ilyayev
authors.forename: Alexander
authors.initials: A
authors.lastname: Stojadinovic
authors.forename: Mina
authors.initials: M
authors.lastname: Izadjoo
authors.forename: Marina
authors.initials: M
authors.lastname: Roistacher
authors.forename: Vera
authors.initials: V
authors.lastname: Pavlov
authors.forename: Victoria
authors.initials: V
authors.lastname: Tzivin
authors.forename: David
authors.initials: D
authors.lastname: Halle
authors.forename: Honguang
authors.initials: H
authors.lastname: Pan
authors.forename: Barry
authors.initials: B
authors.lastname: Trink
authors.forename: Ali O
authors.initials: AO
authors.lastname: Gure
authors.forename: Aviram
authors.initials: A
authors.lastname: Nissan
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D016022:Case-Control Studies; D003106:Colon / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010534:Peritoneal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: C579842:CCAT1 long noncoding RNA, human; D062085:RNA, Long Noncoding; D012333:RNA, Messenger