title: Quantitative proteomics reveal up-regulated protein expression of the SET complex associated with hepatocellular carcinoma.
abstract: We combined culture-derived isotope tags (CDITs) with two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS) to extensively survey abnormal protein expression associated with hepatocellular carcinoma (HCC) in clinical tissues. This approach yielded an in-depth quantitated proteome of 1360 proteins. Importantly, 267 proteins were significantly regulated with a fold-change of at least 1.5. The proteins up-regulated in HCC tissues are involved in regulatory processes, such as the granzyme A-mediated apoptosis pathway (The GzmA pathway). The SET complex, a central component in the GzmA pathway, was significantly up-regulated in HCC tissue. The elevated expressions of all of the SET complex components were validated by Western blotting. Among them, ANP32A and APEX1 were further investigated by immunohistochemistry staining using tissue microarrays (59 cases), confirming their overexpression in tumors. The up-regulation and nuclear accumulations of APEX1 was associated not only with HCC malignancy but also with HCC differentiation in 96 clinical HCC cases. Our work provided a systematic and quantitative analysis and demonstrated key changes in clinical HCC tissues. These proteomic signatures could help to unveil the underlying mechanisms of hepatocarcinogenesis and may be useful for the discovery of candidate biomarkers.
authors.affiliation: Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai 200031, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.forename: Hong-Qiang
authors.initials: HQ
authors.lastname: Ruan
authors.forename: Yan-Sheng
authors.initials: YS
authors.lastname: Liu
authors.forename: Meng-Jie
authors.initials: MJ
authors.lastname: Xu
authors.forename: Jie
authors.initials: J
authors.lastname: Dai
authors.forename: Quan-Hu
authors.initials: QH
authors.lastname: Sheng
authors.forename: Ye-Xiong
authors.initials: YX
authors.lastname: Tan
authors.forename: Zhen-Zhen
authors.initials: ZZ
authors.lastname: Yao
authors.forename: Hong-Yang
authors.initials: HY
authors.lastname: Wang
authors.forename: Jia-Rui
authors.initials: JR
authors.lastname: Wu
authors.forename: Rong
authors.initials: R
authors.lastname: Zeng
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D002853:Chromatography, Liquid; D016000:Cluster Analysis; D004268:DNA-Binding Proteins; D030562:Databases, Protein; D056945:Hep G2 Cells; D056488:Histone Chaperones / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008113:Liver Neoplasms / Q000737:chemistry / Q000378:metabolism*; D010641:Phenotype; D040901:Proteomics / Q000379:methods*; D053719:Tandem Mass Spectrometry; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; C513473:SET protein, human; D014157:Transcription Factors