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Digestive Diseases and Sciences

, Volume 64, Issue 10, pp 2830–2842 | Cite as

Comprehensive Analysis of the Canonical and Non-canonical Wnt Signaling Pathways in Gastric Cancer

  • Le Wang
  • Hao Wang
  • Xianglong Duan
  • Penggao DaiEmail author
  • Jianping LiEmail author
Original Article

Abstract

Background

Previous studies showed that dysregulation of Wnt signaling by gene mutation and abnormal gene expression is one of the causative factors for gastric cancer (GC). So far, a systematic and comprehensive analysis of gene mutation, gene expression, and DNA methylation profiles of the Wnt pathway associated with gastric carcinogenesis, however, has not yet been reported.

Aims

To this end, we investigated all the above-mentioned genetic alterations associated with the canonical and non-canonical Wnt pathways in GC tumors, in order to understand the molecular mechanism underlying gastric carcinogenesis.

Methods

The information on gene mutations and expression was obtained from data resources, such as TCGA, GSEA, and TCGA-STAD, and was analyzed with the cBioPortal platform. We also performed in vitro analysis on DDK2 gene, a Wnt inhibitor, to characterize its role in GC tumor cells.

Results

We found that gene mutations of 43 Wnt genes and abnormal expression of 13 Wnt genes occurred at a high frequency in GC tumors, and gene amplification and deletion are the major mutation types. Clusters of DNA methylation associated with Wnt signaling genes and GC tumors were also revealed, and a significant increase in β-catenin activity was found in the hypermethylated group of GC tumors. In addition, overexpression of DKK2 gene significantly inhibited multiple biological processes of the GC cells, including their growth, clonal forming, migration, and invasion ability, and induced apoptosis of the GC cells.

Conclusions

Our current study suggested that gene mutation, abnormal gene expression, and altered DNA methylation profiles associated with the Wnt signaling may play an important role in gastric carcinogenesis, and DKK2 gene may act as a tumor suppressor in gastric cells.

Keywords

Wnt signaling pathway Gene mutation mRNA expression DNA methylation Gastric cancer 

Notes

Funding

This study was funded by the National Natural Science Foundation of China (Grant No. 81760441).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

10620_2019_5606_MOESM1_ESM.doc (280 kb)
Supplementary material 1 (DOC 279 kb)
10620_2019_5606_MOESM2_ESM.xlsx (38 kb)
Supplementary material 2 (XLSX 37 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Oncology, The First Affiliated Hospital of Medical CollegeXi’an Jiaotong UniversityXi’anChina
  2. 2.National Engineering Research Center for Miniaturized Detection Systems, School of Life SciencesNorthwest UniversityXi’anChina
  3. 3.The Second Department of General SurgeryShaanxi Provincial People’s HospitalXi’anChina
  4. 4.Department of General SurgeryThe First Hospital of YulinShaanxiChina
  5. 5.Department of Otolaryngology Xi’an No.4 HospitalXi’anChina

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