title: Low expression of chloride channel accessory 1 predicts a poor prognosis in colorectal cancer.
abstract: BACKGROUND
  Chloride channel accessory 1 (CLCA1) is a CLCA protein that plays a functional role in regulating the differentiation and proliferation of colorectal cancer (CRC) cells. Here we investigated the relationship between the level of CLCA1 and the prognosis of CRC.
  
  
  METHODS
  First, the level of CLCA1 was detected quantitatively in normal and cancerous colonic epithelial tissues with immunohistochemistry. Next, the correlations between CLCA1 expression, pathological tumor features, and the overall survival rate of patients was analyzed. Finally, 3 publicly available data sets from the Gene Expression Omnibus were examined: normal CRC versus early CRC (GSE4107), primary CRC versus metastatic lesions (GSE28702), and low chromosomal instability versus high chromosomal instability (GSE30540).
  
  
  RESULTS
  The expression of CLCA1 was decreased markedly in tumor specimens. CLCA1 expression was correlated significantly with the histological grade (P < .01) and lymph node metastasis (P < .01). A significantly poorer overall survival rate was found in patients with low levels of CLCA1 expression versus those with high expression levels (P < .05). The results confirmed that the low expression of CLCA1 in CRC was highly associated with tumorigenesis, metastasis, and high chromosomal instability. In addition, the loss of CLCA1 disrupted the differentiation of human colon adenocarcinoma cells (Caco-2) in vitro.
  
  
  CONCLUSIONS
  These findings suggest that CLCA1 levels may be a potential predictor of prognosis in primary human CRC. Low expression of CLCA1 predicts disease recurrence and lower survival, and this has implications for the selection of patients most likely to need and benefit from adjuvant chemotherapy.
authors.affiliation: Department of General Surgery, 309th Hospital of the People's Liberation Army, Beijing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Lin
authors.initials: L
authors.lastname: Cao
authors.forename: Jiaen
authors.initials: J
authors.lastname: Liu
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Xu
authors.forename: Gillian
authors.initials: G
authors.lastname: Milne
authors.forename: Wanhei
authors.initials: W
authors.lastname: Chan
authors.forename: Steven D
authors.initials: SD
authors.lastname: Heys
authors.forename: Colin D
authors.initials: CD
authors.lastname: McCaig
authors.forename: Jin
authors.initials: J
authors.lastname: Pu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D018118:Chloride Channels / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C492109:CLCA1 protein, human; D015820:Cadherins; D018118:Chloride Channels; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: cell differentiation; chloride channel accessory 1 (CLCA1) expression; colorectal carcinoma; prognosis