Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel
Journal cover image

An integrative approach identified genes associated with drug response in gastric cancer.

Publication ,  Journal Article
Zhou, J; Yong, W-P; Yap, CS; Vijayaraghavan, A; Sinha, RA; Singh, BK; Xiu, S; Manesh, S; Ngo, A; Lim, A; Ang, C; Xie, C; Wong, FY; Lin, SJ ...
Published in: Carcinogenesis
April 2015

Gastric cancer (GC) is the second leading cause of global cancer mortality worldwide. However, the molecular mechanism underlying its carcinogenesis and drug resistance is not well understood. To identify novel functionally important genes that were differentially expressed due to combinations of genetic and epigenetic changes, we analyzed datasets containing genome-wide mRNA expression, DNA copy number alterations and DNA methylation status from 154 primary GC samples and 47 matched non-neoplastic mucosa tissues from Asian patients. We used concepts of 'within' and 'between' statistical analysis to compare the difference between tumors and controls within each platform, and assessed the correlations between platforms. This 'multi-regulated gene (MRG)' analysis identified 126 differentially expressed genes that underwent a combination of copy number and DNA methylation changes. Most genes were located at genomic loci associated with GC. Statistical enrichment analysis showed that MRGs were enriched for cancer, GC and drug response. We analysed several MRGs that previously had not been associated with GC. Knockdown of DDX27, TH1L or IDH3G sensitized cells to epirubicin or cisplatin, and knockdown of RAI14 reduced cell proliferation. Further studies showed that overexpression of DDX27 reduced epirubicin-induced DNA damage and apoptosis. Levels of DDX27 mRNA and protein were increased in early-stage gastric tumors, and may be a potential diagnostic and prognostic marker for GC. In summary, we used an integrative bioinformatics strategy to identify novel genes that are altered in GC and regulate resistance of GC cells to drugs in vitro.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Carcinogenesis

DOI

EISSN

1460-2180

Publication Date

April 2015

Volume

36

Issue

4

Start / End Page

441 / 451

Location

England

Related Subject Headings

  • Transcription Factors
  • Stomach Neoplasms
  • Retrospective Studies
  • RNA, Small Interfering
  • RNA Interference
  • Prognosis
  • Oncology & Carcinogenesis
  • Nerve Tissue Proteins
  • Humans
  • Histones
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhou, J., Yong, W.-P., Yap, C. S., Vijayaraghavan, A., Sinha, R. A., Singh, B. K., … Goh, L. K. (2015). An integrative approach identified genes associated with drug response in gastric cancer. Carcinogenesis, 36(4), 441–451. https://doi.org/10.1093/carcin/bgv014
Zhou, Jin, Wei-Peng Yong, Chui Sun Yap, Aadhitthya Vijayaraghavan, Rohit Anthony Sinha, Brijesh Kumar Singh, Sam Xiu, et al. “An integrative approach identified genes associated with drug response in gastric cancer.Carcinogenesis 36, no. 4 (April 2015): 441–51. https://doi.org/10.1093/carcin/bgv014.
Zhou J, Yong W-P, Yap CS, Vijayaraghavan A, Sinha RA, Singh BK, et al. An integrative approach identified genes associated with drug response in gastric cancer. Carcinogenesis. 2015 Apr;36(4):441–51.
Zhou, Jin, et al. “An integrative approach identified genes associated with drug response in gastric cancer.Carcinogenesis, vol. 36, no. 4, Apr. 2015, pp. 441–51. Pubmed, doi:10.1093/carcin/bgv014.
Zhou J, Yong W-P, Yap CS, Vijayaraghavan A, Sinha RA, Singh BK, Xiu S, Manesh S, Ngo A, Lim A, Ang C, Xie C, Wong FY, Lin SJ, Wan WK, Tan IB, Flotow H, Tan P, Lim K-H, Yen PM, Goh LK. An integrative approach identified genes associated with drug response in gastric cancer. Carcinogenesis. 2015 Apr;36(4):441–451.
Journal cover image

Published In

Carcinogenesis

DOI

EISSN

1460-2180

Publication Date

April 2015

Volume

36

Issue

4

Start / End Page

441 / 451

Location

England

Related Subject Headings

  • Transcription Factors
  • Stomach Neoplasms
  • Retrospective Studies
  • RNA, Small Interfering
  • RNA Interference
  • Prognosis
  • Oncology & Carcinogenesis
  • Nerve Tissue Proteins
  • Humans
  • Histones