title: Overexpression of MTA1 and loss of KAI-1 and KiSS-1 expressions are associated with invasion, metastasis, and poor-prognosis of gallbladder adenocarcinoma.
abstract: OBJECTIVE
  Over 90% of patients with gallbladder cancer have invasion and/or metastasis when they are diagnosed at the clinic. Such patients usually have an extremely poor prognosis. The molecular mechanism responsible for the high prevalence of invasion and metastasis remains unknown.
  
  
  METHODS
  We investigated the expression of two metastasis-suppression genes--KAI-1 and KiSS-1--and a metastasis-associated gene--MTA1--in 108 adenocarcinomas, 15 gallbladder polyps, 35 chronic cholecystitis tissues, and 46 peritumoral tissues using in situ hybridization or immunohistochemistry.
  
  
  RESULTS
  We demonstrated that positive MTA1 expression was significantly higher whereas positive expressions of KAI-1 and KiSS-1 genes were significantly lower in gallbladder adenocarcinoma than in peritumoral tissues, polyps, and chronic cholecystitis. Positive MTA1 expression was significantly lower, but positive KAI-1 and KiSS-1 expressions were significantly higher in cases with well-differentiated adenocarcinoma, smaller tumor mass, no metastasis of lymph node, and no invasion of regional tissues than in cases having poorly differentiated adenocarcinoma, larger tumor mass, metastasis and invasion. Univariate Kaplan-Meier analysis showed that increased expression of MTA1 and lowered expression of KAI-1 and KiSS-1 were significantly associated with decreased overall survival. Cox regression analysis showed that tumor mass, lymph node metastasis, invasion, and MTA1 expression levels negatively correlated with survival.
  
  
  CONCLUSIONS
  Our study suggested that KAI-1, KiSS-1, and MTA1 might be important biological markers involved in the carcinogenesis, metastasis, and invasion of gallbladder adenocarcinoma, but MTA1 is an independent factor of prognosis.
authors: Wenjun
authors: W
authors: Wang
authors: Zhu-lin
authors: ZL
authors: Yang
authors: Jie-qiong
authors: JQ
authors: Liu
authors: Le-ping
authors: LP
authors: Yang
authors: Xiao-jing
authors: XJ
authors: Yang
authors: Xi
authors: X
authors: Fu
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002764:Cholecystitis / Q000378:metabolism; D015536:Down-Regulation; D055088:Early Detection of Cancer; D005260:Female; D005704:Gallbladder / Q000378:metabolism; D005706:Gallbladder Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051861:Kangai-1 Protein / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D059648:Kisspeptins / Q000235:genetics / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011127:Polyps / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C497688:CD82 protein, human; C106628:KISS1 protein, human; D051861:Kangai-1 Protein; D059648:Kisspeptins; C089320:MTA1 protein, human; D012333:RNA, Messenger; D012097:Repressor Proteins; D015534:Trans-Activators; D006655:Histone Deacetylases