CpG Islands Methylation Analysis of CDH11, EphA5, and HS3ST2 Genes in Gastric Adenocarcinoma Patients

Abstract

Purpose

Gastric cancer is an aggressive disease which is the fourth prevalent malignancy in the world. Beside the genetic factors, epigenetic alterations such as promoter CpG island hyper methylation are involved in the emergence of gastric cancer. Herein, we investigated the methylation status of CDH11, EphA5, and HS3ST2 genes in patients with and without gastric adenocarcinoma for the first time.

Methods

In the study 40 paraffin-embedded tissue sections from gastric adenocarcinoma patients and 40 specimens from patients with functional dyspepsia were taken. DNA extraction was performed using a modified salting out method. Epizen DNA methylation kit was used to the bisulfite DNA conversion. The methylation status of CDH11, EphA5, and HS3ST2 genes were analyzed by methylation-specific PCR (MSP) technique.

Results

Among the 80 specimens, 71 DNA samples were achieved (34 gastric adenocarcinoma patients and 37 control patients). The results showed that CDH11, EphA5, and HS3ST2 genes are methylated in 28 (82.45%), 19 (55.88%), and 26 (76.47%) of 34 DNA samples from gastric adenocarcinoma patients, respectively, whereas, these genes are methylated in 7 (18.91%), 9 (24.32%) and 7 (18.91%) of 37 samples from noncancerous patients, respectively. Statistical analyses using a chi-squared test showed that there is a statistically significant difference in methylation level of CDH11, EphA5, and HS3ST2 genes between gastric cancer and uncancerous patients (p < 0.05).

Conclusion

To the best of our knowledge, this is the first report on methylation of CDH11, EphA5, and HS3ST2 promoters’ in gastric adenocarcinoma patients using MSP. Identification of novel cancer-related molecular mechanisms can be useful in detection of new treatment strategies.

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Acknowledgements

This work was funded and supported by Liver and Gastrointestinal Diseases Research Center of Tabriz University of Medical Sciences (Grantnumber: 61877) and Molecular Medicine Research Center, Bio‐medicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.

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Correspondence to Bita Sepehri.

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The present study was approved by the Ethics and Research Committees of the Tabriz University of Medical Sciences.

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The authors report no conflicts of interest in this work.

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Eyvazi, S., Khamaneh, A.M., Tarhriz, V. et al. CpG Islands Methylation Analysis of CDH11, EphA5, and HS3ST2 Genes in Gastric Adenocarcinoma Patients. J Gastrointest Canc 51, 579–583 (2020). https://doi.org/10.1007/s12029-019-00290-1

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Keywords

  • Gastric adenocarcinoma
  • Hyper methylation
  • MSP
  • CDH11
  • EphA5
  • HS3ST2