Dataset Information

Deciphering the Protein-Protein Interaction Network Regulating Hepatocelluler Carcinoma Metastasis

ABSTRACT: Hepatocellular carcinoma (HCC) is one of the leading causes of mortality related to cancer all over the world. The poor prognosis of HCC is mostly due to recurrence and tumor metastasis. In order to better understand the molecular mechanisms of HCC metastasis, we analyzed the proteome of three HCC cell lines with different metastasis potentials by using quantitative proteomics and bioinformatics analysis. As a result, we identified 331 cellular proteins potentially associated to HCC metastasis, and constructed a highly connected protein-protein interaction (PPI) network. Functional annotation of the network uncovered prominent pathways and key roles of these proteins, suggesting that metabolism and cytoskeleton biological progresses are greatly involved with HCC metastasis. Furthermore, integrative network analysis revealed a rich-club organization in the PPI network indicating a hub center of connections, including several well-known cancer related proteins, such as SRC proto-oncogene, non-receptor tyrosine kinase (SRC) and pyruvate kinase M2 (PKM2). Moreover, the differential expressions of two identified proteins, including PKM2 and actin-related protein 2/3 complex subunit 4 (ARPC4), were validated using Western blotting. These two proteins were identified as potential prognostic markers for HCC by using survival rate analysis.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Ruibing Chen

LAB HEAD: Chen Ruibing

PROVIDER: PXD005647 | Pride | 2017-06-20

REPOSITORIES: Pride

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Deciphering the protein-protein interaction network regulating hepatocellular carcinoma metastasis.

Qin Guoxuan G Dang Mengjiao M Gao Huajun H Wang Hao H Luo Fengting F Chen Ruibing R

Biochimica et biophysica acta. Proteins and proteomics 20170614 9

Hepatocellular carcinoma (HCC) is one of the leading causes of mortality related to cancer all over the world. To better understand the molecular mechanisms of HCC metastasis, we analyzed the proteome of three HCC cell lines with different metastasis potentials by quantitative proteomics and bioinformatics analysis. As a result, we identified 378 cellular proteins potentially associated to HCC metastasis, and constructed a highly connected protein-protein interaction (PPI) network. Functional an ...[more]

PMID: 28627476

Publication: 1/2

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Project description:Hepatocellular carcinoma (HCC) is the most common liver cancer and a highly malignant tumor. The frequent activation of Ras signaling pathway and the male prevalence are the distinct characteristics of HCC though the underlying mechanisms remain elucidated. By exploring a mouse model of HCC induced by hepatocyte-specific expression of the Hras12V oncogene and showed significant male prevalence in hepatic tumorigenesis, we performed a high-throughput comparative proteomic analysis based on tandem-mass-tag (TMT) labeling combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) on the protein samples from hepatic tumor tissues (T) and peri-tumor tissues (P) of transgenic males and females and the corresponding normal liver tissues (W) of non-transgenic males and females. In total, 5733 proteins were confidently identified, of which 5193 proteins were quantified. Finally, 1344 differentially expressed proteins (DEPs) (quantified in all examined samples; 1.5 ≤ quantitative ratios ≤ 0.67; p ≤ 0.05) were selected for further analysis. Vertical comparison within W, P, T of males and females, respectively, showed that the numbers of DEPs in males were much higher than females. Bioinformatics analyses showed the common and unique cluster enriched items between sexes which indicates the common and gender disparity pathways towards HCC. Further expression change pattern analysis revealed HCC positive/negative-related and Ras oncogene positive/negative-related DEPs. Horizontal comparison between males and females showed that Ras oncogene gradually and significantly reduced the responses to sex hormones from hepatocytes to hepatoma cells and therefore shrunk their gender disparity, which may contribute to the cause of the loss of HCC clinical responses to the therapeutic approaches targeting sex hormone pathways. Additionally, FABP5 was found to be a more sensitive biomarker for clinical diagnose and prognosis prediction of HCC patients comparing to AFP. In conclusion, the present study firstly provided a comprehensive proteome profiles and novel insights in male bias hepatic tumorigenesis induced by H-ras12V oncogene.

			Action	DRS
	HCC_2D_1_1.msf	Msf
	HCC_2D_1_10_1.raw	Raw
	HCC_2D_1_10_2.raw	Raw
	HCC_2D_1_11_1.raw	Raw
	HCC_2D_1_11_2.raw	Raw