Expression deregulation of DNA repair pathway genes in gastric cancer

Shahzad Yousaf, Asad Ullah Khan, Zertashia Akram, Mahmood Akhtar Kayani, Iram Nadeem, Bilquis Begum, Ishrat Mahjabeen

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

This study was designed to check correlation of mRNA and protein expression of BER pathway genes(XRCC1, OGG1) and a proliferation marker (Ki-67) in 100 gastric tissue samples and controls (adjacent uninvolved area). The expression was estimated usingreal time PCR and immunohistochemistry. Genomic instability was also calculated in the same study cohort using 8-OHdG assay, DNA fragmentation assay and comet assay. A significant downregulation of XRCC1 (p < 0.0001) and OGG1 (p < 0.0001) expression was observed in gastric cancer tumors vs controls. When analyzed with spearman correlation, significant positive correlation was observed between OGG1 vs XRCC1 (r = 0.319*, p < 0.02) and significant negative correlation was observed between OGG1 vs Ki-67 (r = −0.462**, p < 0.001) and XRCC1 vs Ki-67 (r = −0.589**, p < 0.001) in gastric cancer tumors. Significantly higher level of 8-OHdG, when compared to controls, was observed in gastric cancer tumors (p < 0.0001). DNA fragmentation assay and comet assay showed the formation of increased ladder patterns and comets in gastric cancer tumors when compared with controls These findings suggest that dysregulation of XRCC1, OGG1 combined with overexpression of Ki-67 may contribute to progression of gastric cancer and may help to sub-classify patients within diverse risk groups for therapeutic advantages.

Original languageEnglish (US)
Pages (from-to)39-50
Number of pages12
JournalCancer Genetics
Volume237
DOIs
StatePublished - Sep 2019
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by the grants from the Higher Education Commission ( HEC ) of Pakistan, as well as the COMSATS University (CUI) Islamabad. All authors would like to acknowledge the patients and normal individuals who contributed to this research work; we also acknowledge hospital staff, Holy family hospital, Pakistan, for their cooperation.

Funding Information:
The authors declare that they have no conflict of interests. This study was supported by the grants from the Higher Education Commission (HEC) of Pakistan, as well as the COMSATS University (CUI) Islamabad. All authors would like to acknowledge the patients and normal individuals who contributed to this research work; we also acknowledge hospital staff, Holy family hospital, Pakistan, for their cooperation.

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

  • BER pathway
  • DNA fragmentation
  • Gastric cancer
  • OGG1
  • Proliferation
  • XRCC1

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