Proteomic profiling of proteins dysregulted in Chinese esophageal squamous cell carcinoma.
Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death in China. In the present study, proteins in tumors and adjacent normal esophageal tissues from 41 patients with ESCC were extracted, and two-dimensional electrophoresis (2-DE) was performed using the pH 3-10 and 4-7 immobilized pH gradient strips. The protein spots expressed differentially between tumors and normal tissues were identified by matrix-assisted laser desorption/ionization and liquid chromatography electrospray/ionization ion trap mass spectrometry. A total of 22 proteins differentially expressed between ESCC and normal esophageal tissues were identified, in which 17 proteins were upregulated and 5 downregulated in tumors. Biological functions of these proteins are related to cell signal transduction, cell proliferation, cell motility, glycolysis, regulation of transcription, oxidative stress processes, and protein folding. Some of the proteins obtained were confirmed by Western blotting and immunohistochemical staining. We showed that high expression of calreticulin and 78-kDa glucose-regulated protein (GRP78) were correlated with poor prognosis by Kaplan-Meier analysis and log rank analysis. Zinc finger protein 410, annexin V, similar to the ubiquitin-conjugating enzyme E2 variant 1 isoform c, mutant hemoglobin beta chain, TPM4-ALK fusion oncoprotein type 2, similar to heat shock congnate 71-kDa protein, GRP78, and pyruvate kinase M2 (M2-PK) were for the first time observed to be dysregulated in human ESCC tissues. The proteins here identified will contribute to the understanding of the tumorigenesis and progression of Chinese ESCC and may potentially provide useful markers for diagnosis or targets for therapeutic intervention and drug development.
Du
Xiao-Li
XL
State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, PR China.
Hu
Hai
H
Lin
De-Chen
DC
Xia
Shu-Hua
SH
Shen
Xiao-Ming
XM
Zhang
Yu
Y
Luo
Man-Li
ML
Feng
Yan-Bin
YB
Cai
Yan
Y
Xu
Xin
X
Han
Ya-Ling
YL
Zhan
Qi-Min
QM
Wang
Ming-Rong
MR
D044466:Asian People; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000208:ethnology / Q000378:metabolism*; D002681:China; D002853:Chromatography, Liquid; D015180:Electrophoresis, Gel, Two-Dimensional; D000091342:Endoplasmic Reticulum Chaperone BiP; D004938:Esophageal Neoplasms / Q000208:ethnology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D020543:Proteome