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.
Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore, Singapore 169610, Singapore.
Tiannan
T
Guo
Sze Sing
SS
Lee
Wai Har
WH
Ng
Yi
Y
Zhu
Chee Sian
CS
Gan
Jiang
J
Zhu
Haixia
H
Wang
Shiang
S
Huang
Siu Kwan
SK
Sze
Oi Lian
OL
Kon
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