Downregulation of the Genes Involved in Reprogramming (SOX2, c-MYC, miR-302, miR-145, and P21) in Gastric Adenocarcinoma

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• 作者：Mitra Khalili ; Mohammad Vasei ; Davood Khalili…
• 关键词：Reprogramming ; Cancer stem cell ; SOX2 ; miR ; 302b ; miR ; 145 ; P21 ; Gastric cancer
• 刊名：Journal of Gastrointestinal Cancer
• 出版年：2015
• 出版时间：September 2015
• 年：2015
• 卷：46
• 期：3
• 页码：251-258
• 全文大小：6,118 KB
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• 作者单位：Mitra Khalili (1)
  Mohammad Vasei (2)
  Davood Khalili (3)
  Kamran Alimoghaddam (4)
  Majid Sadeghizadeh (5)
  Seyed Javad Mowla (5)
  
  1. Department of Medical Genetics and Molecular Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
  2. Department of Pathology and Digestive disease research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
  3. Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  4. Hematology-Oncology and Stem Cell Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
  5. Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, P.O. Box: 14115-154, Tehran, Iran
  
• 刊物主题：Oncology; Gastroenterology; Radiotherapy; Cancer Research; Internal Medicine;
• 出版者：Springer US
• ISSN：1941-6636

文摘

Purpose 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--2?%, P-lt;-.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.