title: Quantitative proteome analysis reveals the correlation between endocytosis-associated proteins and hepatocellular carcinoma dedifferentiation.
abstract: The majority of poorly differentiated hepatocellular carcinomas (HCCs) develop from well-differentiated tumors. Endocytosis is a cellular function which is likely to take part in this development due to its important role in regulating the abundances of vital signaling receptors. Here, we aimed to investigate the abundance of endocytosis-associated proteins in HCCs with various differentiation grades. Therefore, we analyzed 36 tissue specimens from HCC patients via LC-MS/MS-based label-free quantitative proteomics including 19 HCC tissue samples with different degrees of histological grades and corresponding non-tumorous tissue controls. As a result, 277 proteins were differentially regulated between well-differentiated tumors and controls. In moderately and poorly differentiated tumors, 278 and 1181 proteins, respectively, were significantly differentially regulated compared to non-tumorous tissue. We explored the regulated proteins based on their functions and identified thirty endocytosis-associated proteins, mostly overexpressed in poorly differentiated tumors. These included proteins that have been shown to be up-regulated in HCC like clathrin heavy chain-1 (CLTC) as well as unknown proteins, such as secretory carrier-associated membrane protein 3 (SCAMP3). The abundances of SCAMP3 and CLTC were immunohistochemically examined in tissue sections of 84 HCC patients. We demonstrate the novel association of several endocytosis-associated proteins, in particular, SCAMP3 with HCC progression.
authors: Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801 Bochum, Germany. Electronic address: wael.naboulsi@rub.de.
authors: Wael
authors: W
authors: Naboulsi
authors: Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801 Bochum, Germany.
authors: Thilo
authors: T
authors: Bracht
authors: Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801 Bochum, Germany.
authors: Dominik A
authors: DA
authors: Megger
authors: Institute of Pathology, University of Duisburg-Essen, University Hospital Essen, 45147 Essen, Germany.
authors: Henning
authors: H
authors: Reis
authors: Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801 Bochum, Germany.
authors: Maike
authors: M
authors: Ahrens
authors: Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801 Bochum, Germany.
authors: Michael
authors: M
authors: Turewicz
authors: Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801 Bochum, Germany.
authors: Martin
authors: M
authors: Eisenacher
authors: Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801 Bochum, Germany.
authors: Stephanie
authors: S
authors: Tautges
authors: Department of Gastroenterology and Hepatology, University of Duisburg-Essen, University Hospital Essen, 45147 Essen, Germany.
authors: Ali E
authors: AE
authors: Canbay
authors: Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801 Bochum, Germany.
authors: Helmut E
authors: HE
authors: Meyer
authors: Department of General, Visceral and Transplantation Surgery, University of Duisburg-Essen, University Hospital Essen, 45147 Essen, Germany.
authors: Frank
authors: F
authors: Weber
authors: Institute of Pathology, University of Duisburg-Essen, University Hospital Essen, 45147 Essen, Germany.
authors: Hideo A
authors: HA
authors: Baba
authors: Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801 Bochum, Germany. Electronic address: barbara.sitek@rub.de.
authors: Barbara
authors: B
authors: Sitek
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002853:Chromatography, Liquid; D033922:Clathrin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D004705:Endocytosis / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D060787:Neoplasm Grading; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: C543704:CLTC protein, human; D002352:Carrier Proteins; D008565:Membrane Proteins; D020543:Proteome; C109303:SCAMP3 protein, human; D033922:Clathrin Heavy Chains
keywords: CLTC; Endocytosis; Hepatocellular carcinoma; Label-free proteomics; Liver; SCAMP3