{"id":2706,"date":"2014-06-02T07:00:19","date_gmt":"2014-06-02T11:00:19","guid":{"rendered":"http:\/\/admin.acceleratingscience.com\/?p=2706"},"modified":"2017-08-30T18:54:29","modified_gmt":"2017-08-30T18:54:29","slug":"identifying-differential-proteins-in-hepatocellular-carcinoma-using-ms","status":"publish","type":"post","link":"https:\/\/www.thermofisher.com\/blog\/proteomics\/identifying-differential-proteins-in-hepatocellular-carcinoma-using-ms\/","title":{"rendered":"Identifying Differential Proteins in Hepatocellular Carcinoma Using MS"},"content":{"rendered":"<p><img loading=\"lazy\" decoding=\"async\" style=\"float: left; margin: 10px;\" src=\"http:\/\/admin.acceleratingscience.com\/wp-content\/uploads\/2014\/06\/liver_cancer2.jpg\" alt=\"Hepatocellular carcinoma\" width=\"500\" height=\"334\" \/>Hepatocellular carcinoma is one of the most common forms of liver cancer\u00a0and has a poor prognosis. Local ablation therapy with transarterial chemoembolization (TACE), a method whereby the blood supply to the tumor is restricted, is unfortunately\u00a0associated with cholangiocellular differentiation in hepatocellular carcinoma. A potential explanation for this is that TACE provides selection pressure in favor of this particular cell population, which may be resistant to TACE.<sup>1<\/sup>\u00a0In the absence of biomarkers to differentiate between hepatocellular carcinoma and cholangiocarcinoma tumors or any real understanding of the pathogenesis of these types of tumors, treatment is a challenge and options remain few.<\/p>\n<p>Building on their earlier research,<sup>1<\/sup> Zen et al. recently profiled the protein expression of chemo-resistant, mixed-phenotype liver tumors to identify biomarkers for clinical use and better understand the\u00a0pathogenesis of differentiation.<sup>2<\/sup>\u00a0The investigators used 55 human tissue samples from nine different types of liver tissue. The tissue types they used for differentiation were as follows: mixed hepatocellular carcinoma\/cholangiocarcinoma after TACE (the researchers\u00a0examined the areas of hepatocellular carcinoma and areas of cholangiocarcinoma separately), non-treated hepatocellular carcinoma, normal liver parenchyma, normal bile duct, non-treated peripheral cholangiocarcinoma, non-treated hilar\/perihilar cholangiocarcinoma, PSC-associated hilar cholangiocarcinoma, and metastatic colorectal cancer.<\/p>\n<p>The investigators prepared the tissue in\u00a010-\u03bcm thick sections from formalin-fixed, paraffin-embedded tissue blocks before extracting the proteins using centrifugation at\u00a014,000 \u00d7 <em>g <\/em>at 4 \u00baC. Using <a href=\"https:\/\/www.thermofisher.com\/us\/en\/home\/life-science\/protein-biology\/protein-gel-electrophoresis.html\">1D electrophoresis<\/a> gels, they then separated out the proteins by molecular weight and excised the protein band that was visible at 4\u201320% (v\/w) from each lane. Zen et al. took the products post-trypsin digestion and acquired mass spectra using liquid chromatography\u2013tandem mass spectrometry (LC-MS\/MS) on an LTQ Orbitrap Velos hybrid mass spectrometer\u00a0(Thermo Scientific).<\/p>\n<p>In total, Zen and\u00a0team identified 2,864 proteins, of which\u00a02,628 (92%) had at least one unique peptide sequence and 2,009 (70%) of proteins had unique peptide sequences only. They used\u00a0hierarchical clustering\u00a0to build a class hierarchy for tissue types in relation to normalized protein values. The hepatocellular carcinoma and cholangiocarcinoma components of tumors post-TACE had different protein profiles. The research\u00a0showed there were 95 proteins that were significantly modulated\u00a0in the post-TACE hepatocellular carcinoma regions when\u00a0compared\u00a0with the cholangiocarcinoma regions.\u00a0Seventy-eight proteins were up-regulated in hepatocellular carcinoma samples, as compared to 17 up-regulated proteins\u00a0in cholangiocarcinoma tissues.<\/p>\n<p>Although the study did not define the molecular mechanisms behind TACE-induced differentiation in hepatocellular carcinoma, it did identify protein sets\u00a0specific to the hepatocellular carcinoma and cholangiocarcinoma phenotype of post-TACE mixed tumors. In performing this study, Zen et al. have identified potential biomarkers that can be used\u00a0in the differential diagnosis of primary liver tumors.<\/p>\n<p><strong>References<\/strong><\/p>\n<p>1.\u00a0Zen, C. et al. (2011) &#8220;<a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/21491582\" target=\"_blank\" rel=\"noopener\">Mixed phenotype hepatocellular carcinoma after transarterial chemoembolization and liver transplantation<\/a>,&#8221; Liver Transplantation, 17(8) (pp. 943\u2013954).<\/p>\n<p>2. Zen, Y. et al. (2013) &#8220;<a href=\"http:\/\/www.sciencedirect.com\/science\/article\/pii\/S221296851300007X\" target=\"_blank\" rel=\"noopener\">Protein expression profiles of chemo-resistant mixed phenotype liver tumors using laser microdissection and LC\u2013MS\/MS proteomics<\/a>,&#8221; EuPA Open Proteomics, 1 (pp. 38\u201347) .<\/p>\n<p><i>Post Author: Miriam Pollak. Miriam specialised in neuroscience as an undergraduate but traded in lab work for a post graduate degree in science communication.<\/i><\/p>\n<p>She has since had a career that has spanned science communication, science education and communications management.<\/p>\n<p>However, Miriam has found her bliss balancing her love of writing and disseminating medical research with managing a multimillion dollar research budget for a childhood cancer charity in Australia.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Hepatocellular carcinoma is one of the most common forms of liver cancer\u00a0and has a poor prognosis. Local ablation therapy with transarterial chemoembolization (TACE), a method whereby the blood supply to the tumor is restricted, is unfortunately\u00a0associated with cholangiocellular differentiation in hepatocellular carcinoma. A potential explanation for this is that TACE provides selection pressure in favor<\/p>\n","protected":false},"author":7,"featured_media":2705,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_monsterinsights_skip_tracking":false,"_genesis_hide_title":false,"_genesis_hide_breadcrumbs":false,"_genesis_hide_singular_image":false,"_genesis_hide_footer_widgets":false,"_genesis_custom_body_class":"","_genesis_custom_post_class":"","_genesis_layout":"","_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[3],"tags":[184,263,40,214],"division":[],"class_list":{"0":"post-2706","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-cancer-proteomics","8":"tag-cancer-biomarkers","9":"tag-carcinoma","10":"tag-liver-cancer","11":"tag-protein-identification","12":"entry"},"_selected_authors":"","_selected_reviewers":"","acf":[],"yoast_head":"<!-- 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