Global molecular dysfunctions in gastric cancer revealed by an integrated analysis of the phosphoproteome and transcriptome.
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.
Guo
Tiannan
T
Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore, Singapore 169610, Singapore.
Lee
Sze Sing
SS
Ng
Wai Har
WH
Zhu
Yi
Y
Gan
Chee Sian
CS
Zhu
Jiang
J
Wang
Haixia
H
Huang
Shiang
S
Sze
Siu Kwan
SK
Kon
Oi Lian
OL
D045744:Cell Line, Tumor; D008401:Gas Chromatography-Mass Spectrometry; D020869:Gene Expression Profiling; D006801:Humans; D020543:Proteome / Q000235:genetics*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000503:physiopathology*
D020543:Proteome