Downregulation of the Genes Involved in Reprogramming (Sox2, C-Myc, Mir-302, Mir-145, and P21) in Gastric Adenocarcinoma Publisher Pubmed



Khalili M¹ ; Vasei M² ; Khalili D³ ; Alimoghaddam K⁴ ; Sadeghizadeh M⁵ ; Mowla SJ⁵
Source: Journal of Gastrointestinal Cancer Published:2015

Abstract

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 = 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. © 2015, Springer Science+Business Media New York.