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CDX1/2 and KLF5 Expression and Epigenetic Modulation of Sonic Hedgehog Signaling in Gastric Adenocarcinoma

  • Ali Akbar Samadani
  • Novin Nikbakhsh
  • Hassan Taheri
  • Shahriyar Shafaee
  • Sadegh Fattahi
  • Maryam Pilehchian Langroudi
  • Karimollah Hajian
  • Haleh Akhavan-NiakiEmail author
Original Article
  • 62 Downloads

Abstract

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.

Keywords

Gastric cancer DNA methylation Gene expression Epigenetics 

Abbreviations

cDNA

complementary DNA

CDX1/2

caudal type homeobox 1/2

GC

gastric cancer

KLF5

kruppel like factor 5

PCR

polymerase chain reaction

Notes

Acknowledgments

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.

Informed Consent

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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Copyright information

© Arányi Lajos Foundation 2019

Authors and Affiliations

  • Ali Akbar Samadani
    • 1
    • 2
  • Novin Nikbakhsh
    • 3
  • Hassan Taheri
    • 4
  • Shahriyar Shafaee
    • 5
  • Sadegh Fattahi
    • 1
  • Maryam Pilehchian Langroudi
    • 1
  • Karimollah Hajian
    • 6
  • Haleh Akhavan-Niaki
    • 1
    • 7
    Email author
  1. 1.Cellular and Molecular Biology Research Center, Health Research InstituteBabol University of Medical SciencesBabolIran
  2. 2.Gastrointestinal and liver diseases research center (GLDRC)Guilan University of Medical SciencesRashtIran
  3. 3.Department of Surgery, Cancer Research CenterBabol University of Medical SciencesBabolIran
  4. 4.Department of GastroenterologyBabol University of Medical SciencesBabolIran
  5. 5.Department of PathologyBabol University of Medical SciencesBabolIran
  6. 6.Department of Social medicine and statistics, Faculty of MedicineBabol University of Medical SciencesBabolIran
  7. 7.Department of Genetics, Faculty of MedicineBabol University of Medical SciencesBabolIran

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