CDX1/2 and KLF5 Expression and Epigenetic Modulation of Sonic Hedgehog Signaling in Gastric Adenocarcinoma
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Gastric cancer is among the commonplace causes of cancer death worldwide. Sonic hedgehog (Shh) signaling is an important pathway which may be dysregulated in many cancers.CDX1/2, and KLF5are key transcription factors involved in Shh pathway and cancer stem cells. The aim of this study was to investigate the expression and epigenetic alterations of these genes in gastric cancer patients. DNA methylation’s modifications of CDX1, KLF5 and CDX2 genes alongside with the expressions of these genes in gastric cancer tissues and their non-tumoral counterparts (margin tissues) were analyzed using methylation specific sequencing, and Real time PCR Taq man assays, respectively. The expression of CDX1 (P = 0.002) and KLF5 (P = 0.010) were decreased significantly, but it was considerably increased for CDX2 (P = 0.001). Relatively, the results for the regulatory region methylation status of each CpG site had shown a notable fluctuation in these genes with no significant difference in most places. The creation of metastatic lymph nodes in patients was significantly associated with increased expression of CDX2 gene. The modifications of these genes expression can be considered as a cancer biomarker in future studies. Methylation of the investigated genes is not the main mechanism of gastric cancer development.
KeywordsGastric cancer DNA methylation Gene expression Epigenetics
caudal type homeobox 1/2
kruppel like factor 5
polymerase chain reaction
This work was supported by the Research deputy of Babol University of Medical Sciences (Grant No 9237527), and a grant by Iranian National Science Foundation (INSF project code: 92017552). Authors appreciate the staffs of Cellular and Molecular Biology Research Center, Rouhani and Shahid Beheshti hospitals, Razi Medical Laboratory, and all patients who participated in this project.
Compliance with Ethical Standards
Institutional Review Board
This study was approved by the ethics committee of Babol University of Medical Sciences, Iran.
Written informed consent was obtained for all subjects before their inclusion in the study. All experiments and data comparisons were carried out in compliance with relevant laws and guidelines and in accordance with the ethical standards of the Declaration of Helsinki.
Conflict of Interest
The authors declare that they have no conflict of interest.
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