title: Quantitative proteomics by SWATH-MS reveals sophisticated metabolic reprogramming in hepatocellular carcinoma tissues.
abstract: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and understanding its molecular pathogenesis is pivotal to managing this disease. Sequential window acquisition of all theoretical mass spectra (SWATH-MS) is an optimal proteomic strategy to seek crucial proteins involved in HCC development and progression. In this study, a quantitative proteomic study of tumour and adjacent non-tumour liver tissues was performed using a SWATH-MS strategy. In total, 4,216 proteins were reliably quantified, and 338 were differentially expressed, with 191 proteins up-regulated and 147 down-regulated in HCC tissues compared with adjacent non-tumourous tissues. Functional analysis revealed distinct pathway enrichment of up- and down-regulated proteins. The most significantly down-regulated proteins were involved in metabolic pathways. Notably, our study revealed sophisticated metabolic reprogramming in HCC, including alteration of the pentose phosphate pathway; serine, glycine and sarcosine biosynthesis/metabolism; glycolysis; gluconeogenesis; fatty acid biosynthesis; and fatty acid β-oxidation. Twenty-seven metabolic enzymes, including PCK2, PDH and G6PD, were significantly changed in this study. To our knowledge, this study presents the most complete view of tissue-specific metabolic reprogramming in HCC, identifying hundreds of differentially expressed proteins, which together form a rich resource for novel drug targets or diagnostic biomarker discovery.
authors.affiliation: National Center of Biomedical Analysis, Beijing 100850, China.|Experiment Instrument Plant, Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: National Center of Biomedical Analysis, Beijing 100850, China.
authors.forename: Xinzheng
authors.initials: X
authors.lastname: Wang
authors.affiliation: National Center of Biomedical Analysis, Beijing 100850, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Sang
authors.affiliation: Translational Medicine Center of Stem Cells, 307-Ivy Translational Medicine Center, Laboratory of Oncology, Affiliated Hospital, Academy of Military Medical Sciences, Beijing 100071, China.
authors.forename: Zongcheng
authors.initials: Z
authors.lastname: Li
authors.affiliation: National Center of Biomedical Analysis, Beijing 100850, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: National Center of Biomedical Analysis, Beijing 100850, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Mao
authors.affiliation: Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Yan
authors.affiliation: National Center of Biomedical Analysis, Beijing 100850, China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: National Center of Biomedical Analysis, Beijing 100850, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Wang
authors.affiliation: National Center of Biomedical Analysis, Beijing 100850, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Computational Omics Lab, Center of Computational Biology, Beijing Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Ying
authors.affiliation: National Center of Biomedical Analysis, Beijing 100850, China.
authors.forename: Xuemin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: National Center of Biomedical Analysis, Beijing 100850, China.
authors.forename: Kun
authors.initials: K
authors.lastname: He
authors.affiliation: National Center of Biomedical Analysis, Beijing 100850, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D053858:Metabolic Networks and Pathways; D008875:Middle Aged; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor; D020543:Proteome