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Proteomic profiling of proteins dysregulted in Chinese esophageal squamous cell carcinoma

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Abstract

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.

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Acknowledgment

This study was supported by the State Key Basic Research grant of China (2001CB510208, 2002CB513101, 2004CB518705), Beijing Science Fund (7042038), Specialized Research Fund for the Doctoral Program of Higher Education of China (20050023046), and Program for Changjiang Scholars and Innovative Research Team in University (IRT0416).

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  1. State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College, Chinese Academy of Medical Sciences, P.O. Box 2258, Beijing, 100021, People’s Republic of China

    Xiao-Li Du, Hai Hu, De-Chen Lin, Shu-Hua Xia, Xiao-Ming Shen, Yu Zhang, Man-Li Luo, Yan-Bin Feng, Yan Cai, Xin Xu, Ya-Ling Han, Qi-Min Zhan & Ming-Rong Wang

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  1. Xiao-Li Du
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Du, XL., Hu, H., Lin, DC. et al. Proteomic profiling of proteins dysregulted in Chinese esophageal squamous cell carcinoma. J Mol Med 85, 863–875 (2007). https://doi.org/10.1007/s00109-007-0159-4

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