Cellular and Molecular Life Sciences

, Volume 68, Issue 11, pp 1983–2002 | Cite as

Global molecular dysfunctions in gastric cancer revealed by an integrated analysis of the phosphoproteome and transcriptome

  • Tiannan Guo
  • Sze Sing Lee
  • Wai Har Ng
  • Yi Zhu
  • Chee Sian Gan
  • Jiang Zhu
  • Haixia Wang
  • Shiang Huang
  • Siu Kwan Sze
  • Oi Lian Kon
Research Article

Abstract

We integrated LC-MS/MS-based and protein antibody array-based proteomics with genomics approaches to investigate the phosphoproteome and transcriptome of gastric cancer cell lines and endoscopic gastric biopsies from normal subjects and patients with benign gastritis or gastric cancer. More than 3,000 non-redundant phosphorylation sites in over 1,200 proteins were identified in gastric cancer cells. We correlated phosphoproteome data with transcriptome data sets and reported the expression of 41 protein kinases, 5 phosphatases and 65 phosphorylated mitochondrial proteins in gastric cancer cells. Transcriptional expression levels of 190 phosphorylated proteins were >2-fold higher in gastric cancer cells compared to normal stomach tissue. Pathway analysis demonstrated over-presentation of DNA damage response pathway and underscored critical roles of phosphorylated p53 in gastric cancer. This is the first study to comprehensively report the gastric cancer phosphoproteome. Integrative analysis of the phosphoproteome and transcriptome provided an expansive view of molecular signaling pathways in gastric cancer.

Keywords

Gastric cancer Phosphoproteome Transcriptome Protein antibody array Protein kinase Protein phosphatase Mitochondria DNA damage response 

Abbreviations

RTK

Receptor tyrosine kinase

MS

Mass spectrometry

HPLC

High-performance liquid chromatography

FDR

False discovery rate

ERLIC

Electrostatic repulsion-hydrophilic interaction chromatography

SCX

Strong cation exchange

IMAC

Immobilized metal ion affinity chromatography

DDR

DNA damage response

Supplementary material

18_2010_545_MOESM1_ESM.pdf (377 kb)
Supplementary material 1 (PDF 378 kb)
18_2010_545_MOESM2_ESM.xls (2.3 mb)
Supplementary material 2 (XLS 2,341 kb)

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Copyright information

© Springer Basel AG 2010

Authors and Affiliations

  • Tiannan Guo
    • 1
    • 2
  • Sze Sing Lee
    • 1
  • Wai Har Ng
    • 1
  • Yi Zhu
    • 2
  • Chee Sian Gan
    • 2
  • Jiang Zhu
    • 3
  • Haixia Wang
    • 3
  • Shiang Huang
    • 3
  • Siu Kwan Sze
    • 2
  • Oi Lian Kon
    • 1
  1. 1.Division of Medical Sciences, Humphrey Oei Institute of Cancer ResearchNational Cancer Centre SingaporeSingaporeSingapore
  2. 2.School of Biological SciencesNanyang Technological UniversitySingaporeSingapore
  3. 3.Center for Stem Cell Research and Application, Union HospitalHuazhong University of Science and TechnologyWuhanPeople’s Republic of China

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