title: The prognostic effect of PTEN expression status in colorectal cancer development and evaluation of factors affecting it: miR-21 and promoter methylation.
abstract: BACKGROUND
  PTEN is a tumor suppressor gene which is involved in cellular proliferation, differentiation, and apoptosis. Loss or down-regulation of PTEN plays an important role in human cancers development. In this study, we investigated the effect of miR-21 and promoter methylation on the PTEN expression status in CRC tissues and analyzed association of the PTEN expression status with clinicopathological features in patients with CRC.
  
  
  RESULTS
  The PTEN expression was positively detected in 67.2 % CRC tissues and all adjacent non-cancerous samples. PTEN mRNA level was negatively correlated with miR-21 level (r = -0.595, P < 0.001). PTEN expression was also correlated directly with the PTEN mRNA level (r = 0.583, P < 0.001) and conversely with miR-21 level (r = -0.632, P < 0.001). PTEN Promoter methylation was significantly associated with PTEN expression status (p = 0.013). PTEN expression was negatively associated with tumor size (p = 0.007) and advanced tumor stage (P = 0.011). Multivariate analysis indicated that tumor stage, tumor differentiation and PTEN expression status were independent prognostic factors for overall carcinoma in CRC patients (P < 0.05). The Kaplan-Meier curve indicated a negative correlation between PTEN expression levels and survival of CRC patients (P = 0.013).
  
  
  CONCLUSIONS
  This study suggests a high frequency of miR-21 overexpression and aberrant promoter methylation in down-regulation of PTEN expression in colorectal carcinoma. Loss of PTEN may be a prognostic factor for patients with CRC.
authors.affiliation: Infectious Diseases Research Center and Laboratory Science Research Center, Golestan University of Medical Sciences, Gorgan, Iran. yazdani@goums.ac.ir.
authors.forename: Yaghoub
authors.initials: Y
authors.lastname: Yazdani
authors.affiliation: Infectious Diseases Research Center and Laboratory Science Research Center, Golestan University of Medical Sciences, Gorgan, Iran. tourajf@yahoo.com.|Student Research Committee, Golestan University of Medical Sciences, P.O. Box: 4934174611, Gorgan, Iran. tourajf@yahoo.com.
authors.forename: Touraj
authors.initials: T
authors.lastname: Farazmandfar
authors.affiliation: Department of Internal Medicine, Mazandaran University of Medical sciences, Sari, Iran. hosseinazadeh5@gmail.com.
authors.forename: Hossein
authors.initials: H
authors.lastname: Azadeh
authors.affiliation: Department of Genetics, Tehran Medical Sciences branch, Islamic Azad University, Tehran, Iran. zekavat1983@yahoo.com.
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Zekavatian
mesh_terms: D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012334:RNA, Neoplasm / Q000378:metabolism*
chemical_list: D004273:DNA, Neoplasm; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human