Integrative analysis to select cancer candidate biomarkers to targeted validation

Autor(es):Mostrar menos -

Kawahara, Rebeca ^[1] ; Meirelles, Gabriela V. ^[1] ; Heberle, Henry ^[2] ; Domingues, Romenia R. ^[1] ; Granato, Daniela C. ^[1] ; Yokoo, Sami ^[1] ; Canevarolo, Rafael R. ^{[3, 1]} ; Winck, FlaviaV. ^[1] ; Ribeiro, Ana Carolina P. ^[4] ; Brandao, Thais Bianca ^[4] ; Filgueiras, Paulo R. ^[5] ; Cruz, Karen S. P. ^[6] ; Barbuto, Jose Alexandre ^[6] ; Poppi, Ronei J. ^[5] ; Minghim, Rosane ^[2] ; Telles, Guilherme P. ^[7] ; Fonseca, Felipe Paiva ^[8] ; Fox, Jay W. ^[9] ; Santos-Silva, Alan R. ^[8] ; Coletta, Ricardo D. ^[8] ; Sherman, Nicholas E. ^[9] ; Paes Leme, Adriana F. ^[1]

Afiliação do(s) autor(es)

^[1] CNPEM, LNBio, Lab Nacl Biociencias, Lab Espectrometria Massas, Campinas, SP - Brazil

^[2] Univ Sao Paulo, Inst Ciencias Matemat & Comp, Sao Carlos, SP - Brazil

^[3] Ctr Infantil Boldrini, Campinas, SP - Brazil

^[4] Inst Canc Estado Sao Paulo, Sao Paulo - Brazil

^[5] Univ Estadual Campinas, UNICAMP, Inst Quim, Piracicaba - Brazil

^[6] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508 Sao Paulo - Brazil

^[7] Univ Estadual Campinas, UNICAMP, Inst Comp, Campinas, SP - Brazil

^[8] Univ Estadual Campinas, UNICAMP, Fac Odontol Piracicaba, Piracicaba - Brazil

^[9] Univ Virginia, WM Keck Biomed Mass Spectrometry Lab, Charlottesville, VA - USA

• Tipo de documento: Artigo Científico
• Fonte: ONCOTARGET; v. 6, n. 41, p. 43635-43652, DEC 22 2015.
• Citações Web of Science: 4

Resumo

Targeted proteomics has flourished as the method of choice for prospecting for and validating potential candidate biomarkers in many diseases. However, challenges still remain due to the lack of standardized routines that can prioritize a limited number of proteins to be further validated in human samples. To help researchers identify candidate biomarkers that best characterize their samples under study, a well-designed integrative analysis pipeline, comprising MS-based discovery, feature selection methods, clustering techniques, bioinformatic analyses and targeted approaches was performed using discovery-based proteomic data from the secretomes of three classes of human cell lines (carcinoma, melanoma and non-cancerous). Threeyfeature selection algorithms, namely, Beta-binomial, Nearest Shrunken Centroids (NSC), and Support Vector Machine-Recursive Features Elimination (SVM-RFE), indicated a panel of 137 candidate biomarkers for carcinoma and 271 for melanoma, which were differentially abundant between the tumor classes. We further tested the strength of the pipeline in selecting candidate biomarkers by immunoblotting, human tissue microarrays, label-free targeted MS and functional experiments. In conclusion, the proposed integrative analysis was able to pre-qualify and prioritize candidate biomarkers from discovery-based proteomics to targeted MS. (AU)

• Processo FAPESP: 11/22421-2 - Determinação dos sítios de clivagens de alvos de ADAM-17 recombinante em cultura de células humanas
• Beneficiário: Rebeca Kawahara Sakuma
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 09/54067-3 - EMU: aquisição de um espectrômetro de massas acoplado a cromatografia líquida para permitir ampliar a capacidade de atendimento de usuários e disponibilizar novas tecnologias no Laboratório de Espectrometria de Massas do Centro de Biologia Molecular Estrutural (ABTLUS)
• Beneficiário: Adriana Franco Paes Leme
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 09/53839-2 - Criação do Laboratório de Patologia Digital através do uso do escaneador de lâminas histológicas (Aperio® Scanscope CS)
• Beneficiário: Oslei Paes de Almeida
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 10/19278-0 - Estudo da regulação de ADAMs em câncer oral
• Beneficiário: Adriana Franco Paes Leme
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores