Dataset Information

HCC progression - Quantitative proteome analysis reveals the correlation between endocytosis-associated proteins and hepatocellular carcinoma dedifferentiation

ABSTRACT: Endocytosis is a cellular function which is likely to take part in HCC development due to its important role in regulating the abundances of vital signaling receptors. In this study, we aimed to investigate the expression of endocytosis-associated proteins in HCCs with various differentiation grades. Therefore, we analyzed 36 tissue specimens from HCC patients via label-free LC-MS/MS including 19 HCC tissue samples with different degrees of histological grades and 17 corresponding non-tumorous tissue controls. Following label-free analysis 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.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Liver

DISEASE(S): Hepatocellular Carcinoma

SUBMITTER: Wael Naboulsi

LAB HEAD: Barbara Sitek

PROVIDER: PXD003552 | Pride | 2016-09-27

REPOSITORIES: Pride

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Quantitative proteome analysis reveals the correlation between endocytosis-associated proteins and hepatocellular carcinoma dedifferentiation.

Naboulsi Wael W Bracht Thilo T Megger Dominik A DA Reis Henning H Ahrens Maike M Turewicz Michael M Eisenacher Martin M Tautges Stephanie S Canbay Ali E AE Meyer Helmut E HE Weber Frank F Baba Hideo A HA Sitek Barbara B

Biochimica et biophysica acta 20160809 11

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 quan ...[more]

PMID: 27519163

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Project description:Mouse models of hepatocellular carcinoma (HCC) simulate specific subgroups of human HCC. We investigated hepatocarcinogenesis in Mdr2-KO mice, a model of inflammation-associated HCC, using gene expression profiling and immunohistochemical analyses. Gene expression profiling demonstrated that although Mdr2-KO mice differ from other published murine HCC models, they share several important deregulated pathways and many coordinately differentially expressed genes with human HCC datasets. Analysis of genome positions of differentially expressed genes in liver tumors revealed a prolonged region of down-regulated genes on murine chromosome 8 in three of the six analyzed tumor samples. This region is syntenic to human chromosomal regions that are frequently deleted in human HCC and harbor multiple tumor suppressor genes. Real-time RT-PCR analysis of 16 tumor samples confirmed down-regulation of several tumor suppressors in most tumors. We demonstrate that in the aged Mdr2-KO mice, cyclin D1 nuclear level is increased in dysplastic hepatocytes that do not form nodules; however, it is decreased in dysplastic nodules and in liver tumors. We found that this decrease is mostly at the protein, rather than the mRNA level. These findings raise the question on the role of cyclin D1 at early stages of hepatocarcinogenesis in the Mdr2-KO HCC model. Furthermore, we show that most liver tumors in Mdr2-KO mice were characterized by the absence of b-catenin activation. In conclusion, the Mdr2-KO mouse may serve as a model for b-catenin-negative subgroup of human HCCs characterized by low nuclear cyclin D1 levels in tumor cells and by down-regulation of multiple tumor suppressor genes. Experiment Overall Design: The liver RNA samples from six Mdr2-KO tumors, six non-tumorous liver tissues (four matched and two unmatched), as well as from three control heterozygous mice at 16 months of age were subjected to gene expression profiling using the genome scale Affymetrix Mouse Genome 430 2.0 Array.

Project description:Chronic infections by hepatitis B virus (HBV) and hepatitis C virus (HCV) appear to be the most significant causes of hepatocellular carcinoma (HCC). Aberrant promoter methylation is known to be deeply involved in cancer, including HCC. In this study, we analyzed aberrant promoter methylation on genome-wide scale in 6 HCCs including 3 HBV-related and 3 HCV-related HCCs, 6 matched noncancerous liver tissues and 3 normal liver tissues by methylated DNA immunoprecipitation-on-chip analysis. Candidate genes with promoter methylation were detected more frequently in HCV-related HCC. Candidate genes methylated preferentially to HBV-related or HCV-related HCCs were detected and selected, and methylation levels of the selected genes were validated using 125 liver tissue samples, including 61 HCCs (28 HBV-related HCCs and 33 HCV-related HCCs) and matched 59 matched noncancerous livers, and 5 normal livers, by quantitative methylation analysis using MALDI-TOF mass spectrometry. Among analyzed genes, preferential methylation in HBV-related HCC was validated in 1 gene only. However, 15 genes were found methylated preferentially in HCV-related HCC, which was independent from age. Hierarchical clustering of HCC using these 15 genes stratified HCV-related HCC as a cluster of frequently methylated samples. The 15 genes included genes inhibitory to cancer-related signaling such as RAS/RAF/ERK and Wnt/b-catenin pathways. It was indicated that genes methylated preferentially in HCV-related HCC exist, and it was suggested that DNA methylation might play an important role in HCV-related HCC by silencing cancer-related pathway inhibitors. we analyzed aberrant promoter methylation in 6 HCC clinical samples (including 3 HBV-related HCCs and 3 HCV-related HCCs) and their matched noncancerous tissues on genome-wide scale by the method. Candidate regions of promoter methylation preferentially to HBV-related HCC and HCV-related HCC were selected, and the methylation levels of these genes were measured quantitatively using MALDI-TOF mass spectrometry. Expression levels of these 6 pairs of HCC and 4 more pairs of HCCs and surrounding noncancerous tissues were analyzed by expression array and are reported in this Series. <br><br>This experiment was reloaded in November 2010 after additional curation. this dataset is part of the TransQST collection.

Dataset Information

HCC progression - Quantitative proteome analysis reveals the correlation between endocytosis-associated proteins and hepatocellular carcinoma dedifferentiation

Publications

Quantitative proteome analysis reveals the correlation between endocytosis-associated proteins and hepatocellular carcinoma dedifferentiation.

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