Construction of a nasopharyngeal carcinoma 2D/MS repository with Open Source XML Database – Xindice

BACKGROUND: Many proteomics initiatives require integration of all information with uniformcriteria from collection of samples and data display to publication of experimental results. The integration and exchanging of these data of different formats and structure imposes a great challenge to us. The XML technology presents a promise in handling this task due to its simplicity and flexibility. Nasopharyngeal carcinoma (NPC) is one of the most common cancers in southern China and Southeast Asia, which has marked geographic and racial differences in incidence. Although there are some cancer proteome databases now, there is still no NPC proteome database. RESULTS: The raw NPC proteome experiment data were captured into one XML document with Human Proteome Markup Language (HUP-ML) editor and imported into native XML database Xindice. The 2D/MS repository of NPC proteome was constructed with Apache, PHP and Xindice to provide access to the database via Internet. On our website, two methods, keyword query and click query, were provided at the same time to access the entries of the NPC proteome database. CONCLUSION: Our 2D/MS repository can be used to share the raw NPC proteomics data that are generated from gel-based proteomics experiments. The database, as well as the PHP source codes for constructing users' own proteome repository, can be accessed at

Construction of a nasopharyngeal carcinoma 2D/MS repository with Open Source XML Database – Xindice-3

<p><b>Copyright information:</b></p><p>Taken from "Construction of a nasopharyngeal carcinoma 2D/MS repository with Open Source XML Database – Xindice"</p><p>Bmc Bioinformatics [Electronic Resource] 2006;7():13-13.</p><p>Published online 11 Jan 2006</p><p>PMCID:PMC1351203.</p><p>Copyright © 2006 Li et al; licensee BioMed Central Ltd.</p>easily

Construction of a nasopharyngeal carcinoma 2D/MS repository with Open Source XML Database – Xindice-4

<p><b>Copyright information:</b></p><p>Taken from "Construction of a nasopharyngeal carcinoma 2D/MS repository with Open Source XML Database – Xindice"</p><p>Bmc Bioinformatics [Electronic Resource] 2006;7():13-13.</p><p>Published online 11 Jan 2006</p><p>PMCID:PMC1351203.</p><p>Copyright © 2006 Li et al; licensee BioMed Central Ltd.</p>tory

Construction of a nasopharyngeal carcinoma 2D/MS repository with Open Source XML Database – Xindice-0

<p><b>Copyright information:</b></p><p>Taken from "Construction of a nasopharyngeal carcinoma 2D/MS repository with Open Source XML Database – Xindice"</p><p>Bmc Bioinformatics [Electronic Resource] 2006;7():13-13.</p><p>Published online 11 Jan 2006</p><p>PMCID:PMC1351203.</p><p>Copyright © 2006 Li et al; licensee BioMed Central Ltd.</p>n XSLT processor. The root of the query result XML document was result tag. Every query record would be inserted among spot tag

Construction of a nasopharyngeal carcinoma 2D/MS repository with Open Source XML Database – Xindice-2

<p><b>Copyright information:</b></p><p>Taken from "Construction of a nasopharyngeal carcinoma 2D/MS repository with Open Source XML Database – Xindice"</p><p>Bmc Bioinformatics [Electronic Resource] 2006;7():13-13.</p><p>Published online 11 Jan 2006</p><p>PMCID:PMC1351203.</p><p>Copyright © 2006 Li et al; licensee BioMed Central Ltd.</p>As shown in the PMF map of glutathione transferase omega 1-1, all monoisotopic peaks could be displayed and used to compare with the user's PMF map

Construction of a nasopharyngeal carcinoma 2D/MS repository with Open Source XML Database – Xindice-1

<p><b>Copyright information:</b></p><p>Taken from "Construction of a nasopharyngeal carcinoma 2D/MS repository with Open Source XML Database – Xindice"</p><p>Bmc Bioinformatics [Electronic Resource] 2006;7():13-13.</p><p>Published online 11 Jan 2006</p><p>PMCID:PMC1351203.</p><p>Copyright © 2006 Li et al; licensee BioMed Central Ltd.</p>ository were provided, one is to click the clickable spot and the other is to query with keyword. The user could see the position of spot on the gel through the hyperlink of ID and other information about the spot such as pI, MW, accession number, scores of Mascot or other database search software and etc. Through the hyperlink of accession number in the NCBI, the user could get more information about this protein directly without searching again in NCBI

Proteomic analysis in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a particular type of head and neck cancer with a strong ethnic and enigmatic epidemiology that long puzzles the scientific society. Despite present all over the world, around 80% of all cases are in Asia where it is endemic, followed by low incidence regions in all other continents. Portugal has the second incidence in Europe for women, and third for men (Globocan 2012) among all European countries. Many efforts have been made to clarify and understand this unique geographic and epidemiologic distribution. The onset and evolution of nasopharyngeal carcinoma is a complex multi-stage process and may take a long time to occur. Although the molecular basis remains uncertain, we know that environmental factors, Epstein-Barr virus (EBV) infection and genetic susceptibility are considered to be the three major contributors. Further examination of these genes’ expression in each tumor revealed that around 93 oncogenes are up regulated in each tumor, while the mean number of TSGs down regulated was 109. In Portugal, the works of Souza & Breda have identified important polymorphism markers that may play a role in the onset and NPC development on the Portuguese northern region population. Despite the efforts made, the molecular mechanisms of NPC carcinogenesis and progression remains to be understood. In this regard, current omics methodologies offer a different approach to identify unique miRNAs and proteins that expression signatures associated with the cancer phenotype, reflecting the biological and pathological grade of the disease. Thus, the discovery of useful NPC biomarkers will lead to new diagnostic and prognostic tools. Meanwhile, the treatment of NPC has evolved in the past two decades. Since 2000, intensity modulated radiation therapy (IMRT) has been widely used to treat nasopharyngeal carcinoma. IMRT provides better dose delivery to the target while sparing the surrounding normal tissues while local control reaches 98% at 4 years24-28. At least one prospective randomized controlled trial showed its benefit in salivary protection in HNC. However, despite the excellent local control, 43% of patients will develop distant metastasis before 5 years and die25-26. In Portugal, IMRT is used at the Instituto Português de Oncologia de Lisboa (IPOLFG) since 2009 and represents the current standard of care for HNC RT, including NPC. Until now, several prognostic markers were identified and investigated for screening, and prognostic tools for NPC, have been purposed, particularly in Asia. However, to our knowledge, there are no validated identified markers to predict distant metastasis or outcome. Moreover, the studies exploring this subject have identified a population-based variety of biomarkers stressing an omic translation of NPC ethnic distribution. At the present work, this research explored formalin-fixed paraffin-embedded samples of biopsied nasopharyngeal carcinoma tumors via proteomic analysis. The aim is to describe a tumor profiling from the studied cohort and discover biomarkers to predict distant metastasis. Secondary endpoints are the discovery of biomarkers related to tumor radioresistance and treatment toxicity. Label-free quantitative mass spectrometry was able to identify 12 up-regulated proteins on early-stage primary tumors that were not present on advanced-stage primaries. Moreover, EBV and HSV co-infection was detected. No signs of HPV-related proteins were seen. Although the clinical outcomes of early and advanced primary tumors were identical, this can be attributed to the known effectiveness of intensive chemoradiation. Moreover, the difference in tumor profiling may reflect that those earlystage tumors could benefit from de-escalation protocols. We were able to detect the presence of a pool of 10 proteins related to distant metastases. Among them, the significant presence of interferon and tyrosine kinase proteins generates the hypothesis that they may represent therapeutic targets. Validation is needed.O carcinoma da nasofaringe (NPC) é um tipo particular de cancro da cabeça e pescoço com um epidemiologia enigmática e forte cariz étnico que há muito intriga a comunidade científica. Apesar de presente em todo o mundo, 805 dos casos encontram-se na Ásia, onde é endémico, seguido de regiões de media e baixa incidência em todos os outros continentes. Portugal tem a segunda incidência em mulheres e a terceira em homens dentre todos os países da Europa (Globocan 2012). Muitos esforços foram realizados para esclarecer e compreender esta distribuição epidemiológica e geográfica. A instalação e evolução do NPC é um processo com múltiplas fases e pode demorar um longo período de tempo para ocorrer. Apesar da base molecular da sua origem permanecer incerta, sabe-se que factores ambientais, a infecção pelo vírus Epstein-Barr e a susceptibilidade genética do hospedeiro são os três maiores contribuidores. Análise aprofundada da expressão genética revelou que cerca de 93 oncogenes estão sobre regulados enquanto que o número médio de genes supressores de tumor down regulated é de cerca de 109. Em Portugal, o trabalho de Souza & Breda identificaram um importante marcador de polimorfismo que pode estar relacionado com a instalação do NPC na população portuguesa na região norte. À despeito dos esforços realizados, o mecanismo molecular da carcinogênese do NPC e sua progressão permanecem por ser esclarecidos. A este respeito, as actuais tecnologias de ômica oferecem uma abordagem diferente capaz de identificar miRNAs e proteínas únicos que expressam assinatura com um fenótipo do cancro, refletindo o grau biológico e patológico da doença. Assim, a descoberta de biomarcadores úteis levará a novas ferramentas prognósticas. Ao mesmo tempo, o tratamento do NPC evoluiu consideravelmente nas últimas duas décadas. Desde 2000, a radioterapia com intensidade modulada do feixe (IMRT) tem sido amplamente utilizada para o tratamento do carcinoma da nasofaringe. IMRT fornece melhor entrega da dose ao alvo enquanto poupa os tecidos adjacentes sadios ao mesmo tempo que o controlo local alcança 98% aos 4 anos (Lee et al, 2002). Pelo menos uma meta-análise demonstrou o benefício na capacidade de proteção salivar em carcinomas da cabeça e pescoço. Entretanto, apesar do excelente controlo local, até 43% dos doentes vão morrer devido às metástases à distância antes dos 5 anos. Em Portugal, IMRT é utilizada no Instituto Português de Oncologia de Lisboa (IPOLFG) desde 2009 e representa o actual estado da arte no tratamento da maioria dos carcinomas da cabeça e pescoço incluindo NPC. Até o momento, diversos marcadores prognósticos de NPC foram propostos, particularmente na Ásia. Contudo, até o momento não são utilizados marcadores validades para predizer metástases ou evolução do doente. Estudos avaliando esta questão identificaram uma população variada de biomarcadores distintos a outras regiões geográficas, ressaltando a diversidade étnica da população dos doentes com NPC. Neste trabalho, esta pesquisa explorou amostras de carcinoma da nasofaringe provenientes de biopsias fixadas em formalina e embebidas em parafina através de análise proteómica. O objectivo é descrever o perfil tumoral da coorte estudada e descobrir biomarcadores capazes de predizer metástases à distância. Objectivos secundários é a descoberta de biomarcadores relacionados ao tumor que determinem radioresistência ou toxicidade ao tratamento. Espectroscopia de massa por ressonância magnética foi capaz de identificar 12 proteínas sobre expressadas nas em tumores primários iniciais que não estão presentes em tumores primários avançados. Além disso, foi detectada uma coinfecção EBV e HSV sem sinais de proteínas relacionadas ao HPV. Apesar dos resultados clínicos terem sido idênticos em ambos os grupos, isto pode ser explicado pela efectividade e intensidade do tratamento combinado. Além disso, a diferença em perfil tumorais podem refletir um perfil de doentes que poderia se beneficiar de protocolos de desintensificação. Esta pesquisa foi capaz de detectar a presença de 10 proteínas relacionadas aos doentes com metástases à distância. Entre elas, a presença de interferon e inibidores da tirosina cinase geram a hipótese de que podem representar potenciais alvos terapêuticos