title: Downregulation of the Genes Involved in Reprogramming (SOX2, c-MYC, miR-302, miR-145, and P21) in Gastric Adenocarcinoma.
abstract: OBJECTIVE
  Many cell signaling pathways essential for normal stem cell development are involved in cancer initiation and progression. In the present study, motivated by a possible contribution of reprogramming process in induction of cancer, we compared the expression level of main genes involved in iPS generation, i.e., miR-302, miR-145, SOX2, c-MYC, and P21, in a series of tumor and non-tumor tissues of stomach.
  
  
  METHODS
  A total number of 34 tumors and their matched non-tumor (as control) gastric surgical specimens were obtained. The expression of the candidate genes was evaluated by using real-time PCR and immunohistochemistry (IHC) techniques.
  
  
  RESULTS
  Our data revealed a significant downregulation of miR-302b, P21, and miR-145 genes in intestinal and SOX2 gene in diffuse type of tumor samples. SOX2, but not the other genes, showed a significant downregulation in both proximal (cardia and fundus) and distal (body and antrum) sites of stomach. Based on receiver-operating characteristic (ROC) analyses, the highest total area under the curve (AUC) was found for SOX2 (AUC = 82 %, P < 0.001). Interestingly, all tumor samples revealed a negative signal for c-MYC expression, while non-tumor samples represented an intense cytoplasmic staining.
  
  
  CONCLUSIONS
  Despite the fact that some hESC-specific genes are upregulated in tumors, our data revealed a significant downregulation of all candidate genes, except for c-MYC, in tumor samples of stomach. Moreover, ROC data demonstrated that SOX2 gene expression index is a better potential biomarker of gastric cancer, compared to other tested genes. SOX2 expression has a good sensitivity and specificity to discriminate correctly between tumor/non-tumor and also high/low grades of tumor malignancy. It seems downregulation of miR-302b, miR-145, and P21 could contribute to gastric tumor initiation and progression.
authors.affiliation: Department of Medical Genetics and Molecular Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
authors.forename: Mitra
authors.initials: M
authors.lastname: Khalili
authors.forename: Mohammad
authors.initials: M
authors.lastname: Vasei
authors.forename: Davood
authors.initials: D
authors.lastname: Khalili
authors.forename: Kamran
authors.initials: K
authors.lastname: Alimoghaddam
authors.forename: Majid
authors.initials: M
authors.lastname: Sadeghizadeh
authors.forename: Seyed Javad
authors.initials: SJ
authors.lastname: Mowla
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D000067470:Cellular Reprogramming Techniques / Q000379:methods*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology