title: KISS1 methylation and expression as predictors of disease progression in colorectal cancer patients.
abstract: OBJECTIVE
  To examine the effect of aberrant methylation of the KISS1 promoter on the development of colorectal cancer (CRC) and to investigate reversing aberrant methylation of the KISS1 promoter as a potential therapeutic target.
  
  
  METHODS
  KISS1 promoter methylation, mRNA expression and protein expression were detected by methylation-specific polymerase chain reaction (PCR), real-time quantitative PCR and Western blotting, respectively, in 126 CRC tissues and 142 normal colorectal tissues. Human CRC cells with KISS1 promoter hypermethylation and poor KISS1 expression were treated in vitro with 5-aza-2'-deoxycytidine (5-Aza-CdR). After treatment, KISS1 promoter methylation, KISS1 mRNA and protein expression and cell migration and invasion were evaluated.
  
  
  RESULTS
  Hypermethylation of KISS1 occurred frequently in CRC samples (83.1%, 105/126), but was infrequent in normal colorectal tissues (6.34%, 9/142). Moreover, KISS1 methylation was associated with tumor differentiation, the depth of invasion, lymph node metastasis and distant metastasis (P < 0.001). KISS1 methylation was also associated with low KISS1 expression (P < 0.001). Furthermore, we observed re-expression of the KISS1 gene and decreased cell migration after 5-Aza-CdR treatment in a CRC cell line.
  
  
  CONCLUSIONS
  These data suggest that KISS1 is down-regulated in cancer tissues via promoter hypermethylation and therefore may represent a candidate target for treating metastatic CRC.
authors.affiliation: Shao-Qin Chen, Zhi-Hua Chen, Su-Yong Lin, Qi-Bao Dai, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China.
authors.forename: Shao-Qin
authors.initials: SQ
authors.lastname: Chen
authors.affiliation: Shao-Qin Chen, Zhi-Hua Chen, Su-Yong Lin, Qi-Bao Dai, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China.
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Chen
authors.affiliation: Shao-Qin Chen, Zhi-Hua Chen, Su-Yong Lin, Qi-Bao Dai, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China.
authors.forename: Su-Yong
authors.initials: SY
authors.lastname: Lin
authors.affiliation: Shao-Qin Chen, Zhi-Hua Chen, Su-Yong Lin, Qi-Bao Dai, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China.
authors.forename: Qi-Bao
authors.initials: QB
authors.lastname: Dai
authors.affiliation: Shao-Qin Chen, Zhi-Hua Chen, Su-Yong Lin, Qi-Bao Dai, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China.
authors.forename: Leng-Xi
authors.initials: LX
authors.lastname: Fu
authors.affiliation: Shao-Qin Chen, Zhi-Hua Chen, Su-Yong Lin, Qi-Bao Dai, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China.
authors.forename: Rui-Qing
authors.initials: RQ
authors.lastname: Chen
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation / Q000187:drug effects; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018450:Disease Progression; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D059648:Kisspeptins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D004791:Enzyme Inhibitors; C106628:KISS1 protein, human; D059648:Kisspeptins; D012333:RNA, Messenger; D015254:DNA Modification Methylases
keywords: 5-aza-2’-deoxycytidine; Colorectal cancer; KISS1; Metastasis; Methylation
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