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

doi:10.1016/j.cancergen.2019.06.002

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 journal › Article › peer-review

10 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 language	English (US)
Pages (from-to)	39-50
Number of pages	12
Journal	Cancer Genetics
Volume	237
DOIs	https://doi.org/10.1016/j.cancergen.2019.06.002
State	Published - Sep 2019
Externally published	Yes

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cancergen.2019.06.002

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@article{d9c64079f4c64b54a7c3838dad73fd71,

title = "Expression deregulation of DNA repair pathway genes in gastric cancer",

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.",

keywords = "BER pathway, DNA fragmentation, Gastric cancer, OGG1, Proliferation, XRCC1",

author = "Shahzad Yousaf and Khan, {Asad Ullah} and Zertashia Akram and Kayani, {Mahmood Akhtar} and Iram Nadeem and Bilquis Begum and Ishrat Mahjabeen",

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: {\textcopyright} 2019 Elsevier Inc.",

year = "2019",

month = sep,

doi = "10.1016/j.cancergen.2019.06.002",

language = "English (US)",

volume = "237",

pages = "39--50",

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AU - Yousaf, Shahzad

AU - Khan, Asad Ullah

AU - Akram, Zertashia

AU - Kayani, Mahmood Akhtar

AU - Nadeem, Iram

AU - Begum, Bilquis

AU - Mahjabeen, Ishrat

N1 - 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.

PY - 2019/9

Y1 - 2019/9

N2 - 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.

AB - 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.

KW - BER pathway

KW - DNA fragmentation

KW - Gastric cancer

KW - OGG1

KW - Proliferation

KW - XRCC1

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SN - 2210-7762

VL - 237

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EP - 50

JO - Cancer genetics

JF - Cancer genetics

ER -

Expression deregulation of DNA repair pathway genes in gastric cancer

Abstract

Bibliographical note

Keywords

UN SDGs

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