Downregulation of the Genes Involved in Reprogramming (SOX2, c-MYC, miR-302, miR-145, and P21) in Gastric Adenocarcinoma
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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.
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.
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.
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.
KeywordsReprogramming Cancer stem cell SOX2 miR-302b miR-145 P21 Gastric cancer
We are grateful to Dr. Forouzandeh Fereidooni, the previous head of the Iran Tumor Bank, Dr. Zahra Hosseini, Dr. Fatemeh Kamali, and Mr. Ahmad Joulaie for supplying clinical samples and providing patients’ clinicopathological information. All clinical samples were provided by Iran National Tumor Bank (which is funded by the Cancer Institute of Tehran University, for cancer research). We also offer special appreciation to Prof. Reza Malekzadeh (Tehran University of Medical Sciences) for worthwhile advisors and Mrs. Rozita Edalat, Mehdi Parniyan and Vahid Kia (Pasteur Institute of Iran) for providing technical advice concerning Real-Time PCR.
Conflict of Interest
The authors have no conflict of interests.
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