Enhanced Interferon Signaling Pathway in Oral Cancer Revealed by Quantitative Proteome Analysis of Microdissected Specimens Using 16O/18O Labeling and Integrated Two-dimensional LC-ESI-MALDI Tandem MS

被引：84

作者：

Chi, Lang-Ming ^{[1
,4
]}

Lee, Chien-Wei ^{[1
]}

Chang, Kai-Ping ^{[5
]}

Hao, Sheng-Po ^{[5
]}

Lee, Hang-Mao ^{[1
]}

Liang, Ying ^{[1
]}

Hsueh, Chuen ^{[1
,6
]}

Yu, Chia-Jung ^{[1
,2
]}

Lee, I-Neng ^{[1
]}

Chang, Yin-Ju ^{[1
]}

Lee, Shih-Ying ^{[1
]}

Yeh, Yuan-Ming ^{[3
]}

Chang, Yu-Sun ^{[1
,3
]}

Chien, Kun-Yi ^{[1
,2
]}

Yu, Jau-Song ^{[1
,2
]}

机构：

[1] Chang Gung Univ, Mol Med Res Ctr, Coll Med, Tao Yuan 333, Taiwan

[2] Chang Gung Univ, Dept Biochem & Mol Biol, Coll Med, Tao Yuan 333, Taiwan

[3] Chang Gung Univ, Grad Inst Biomed Sci, Coll Med, Tao Yuan 333, Taiwan

[4] Chang Gung Mem Hosp, Dept Med Res & Dev, Tao Yuan 333, Taiwan

[5] Chang Gung Mem Hosp, Dept Otolaryngol Head & Neck Surg, Tao Yuan 333, Taiwan

[6] Chang Gung Mem Hosp, Dept Pathol, Tao Yuan 333, Taiwan

来源：

MOLECULAR & CELLULAR PROTEOMICS | 2009年 / 8卷 / 07期

关键词：

SQUAMOUS-CELL CARCINOMA; LASER-CAPTURE MICRODISSECTION; THYMIDINE PHOSPHORYLASE EXPRESSION; MULTIDIMENSIONAL LIQUID-CHROMATOGRAPHY; PANCREATIC DUCTAL ADENOCARCINOMA; EXTRACELLULAR-MATRIX COMPONENTS; APOPTOSIS-INDUCING LIGAND; UBIQUITIN-LIKE PROTEIN; DATA-BASE REPORT; MASS-SPECTROMETRY;

D O I：

10.1074/mcp.M800460-MCP200

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Oral squamous cell carcinoma (OSCC) remains one of the most common cancers worldwide, and the mortality rate of this disease has increased in recent years. No molecular markers are available to assist with the early detection and therapeutic evaluation of OSCC; thus, identification of differentially expressed proteins may assist with the detection of potential disease markers and shed light on the molecular mechanisms of OSCC pathogenesis. We performed a multidimensional O-16/O-18 proteomics analysis using an integrated ESI-ion trap and MALDI-TOF/TOF MS system and a computational data analysis pipeline to identify proteins that are differentially expressed in microdissected OSCC tumor cells relative to adjacent nontumor epithelia. We identified 1233 unique proteins in microdissected oral squamous epithelia obtained from three pairs of OSCC specimens with a false discovery rate of < 3%. Among these, 977 proteins were quantified between tumor and non-tumor cells. Our data revealed 80 dysregulated proteins (53 up-regulated and 27 down-regulated) when a 2.5-fold change was used as the threshold. Immunohistochemical staining and Western blot analyses were performed to confirm the overexpression of 12 up-regulated proteins in OSCC tissues. When the biological roles of 80 differentially expressed proteins were assessed via MetaCore (TM) analysis, the interferon (IFN) signaling pathway emerged as one of the most significantly altered pathways in OSCC. As many as 20% (10 of 53) of the up-regulated proteins belonged to the IFN-stimulated gene (ISG) family, including ubiquitin cross-reactive protein (UCRP)/ISG15. Using head-and-neck cancer tissue microarrays, we determined that UCRP is overexpressed in the majority of cheek and tongue cancers and in several cases of larynx cancer. In addition, we found that IFN-beta stimulates UCRP expression in oral cancer cells and enhances their motility in vitro. Our findings shed new light on OSCC pathogenesis and provide a basis for the future development of novel biomarkers. Molecular & Cellular Proteomics 8: 1453-1474, 2009.

引用

页码：1453 / 1474

页数：22

共 146 条

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