Felipe Paiva Fonseca1, Carolina Carneiro Soares Macedo2, Sara Ferreira Dos Santos Costa3, Adriana Franco Paes Leme4, Romênia Ramos Rodrigues4, Hélder Antônio Rebelo Pontes5, Albina Altemani6, Willie F P van Heerden7, Manoela Domingues Martins8, Oslei Paes de Almeida2, Alan Roger Santos-Silva2, Márcio Ajudarte Lopes2, Pablo Agustin Vargas9. 1. Department of Oral Diagnosis, Oral Pathology Division, Piracicaba Dental School, University of Campinas (UNICAMP), Piracicaba, Brazil; Department of Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. 2. Department of Oral Diagnosis, Oral Pathology Division, Piracicaba Dental School, University of Campinas (UNICAMP), Piracicaba, Brazil. 3. Department of Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. 4. Laboratório de Espectrometria de Massas, Laboratório Nacional de Biociências (LNBio), Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Campinas, Brazil. 5. Service of Oral Pathology, João de Barros Barreto University Hospital, Federal University of Pará, Belém, Brazil. 6. Department of Pathology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil. 7. Department of Oral Pathology and Oral Biology, School of Dentistry, University of Pretoria, Pretoria, South Africa. 8. Department of Oral Diagnosis, Oral Pathology Division, Piracicaba Dental School, University of Campinas (UNICAMP), Piracicaba, Brazil; Department of Pathology, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. 9. Department of Oral Diagnosis, Oral Pathology Division, Piracicaba Dental School, University of Campinas (UNICAMP), Piracicaba, Brazil; Department of Oral Pathology and Oral Biology, School of Dentistry, University of Pretoria, Pretoria, South Africa. Electronic address: pavargas@unicamp.br.
Abstract
OBJECTIVE: The aim of this study was to determine the proteome of adenoid cystic carcinoma (AdCC) and polymorphous adenocarcinoma (PAc) and to identify a protein signature useful in distinguishing these two neoplasms. STUDY DESIGN: Ten cases of AdCC and 10 cases of PAc were microdissected for enrichment of neoplastic tissue. The samples were submitted to liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the proteomics data were analyzed by using the MaxQuant software. LC-MS/MS spectra were searched against the Human UniProt database, and statistical analyses were performed with Perseus software. Bioinformatic analyses were performed by using discovery-based proteomic data on both tumors. RESULTS: LC-MS/MS analysis identified 1957 proteins. The tumors shared 1590 proteins, and 261 were exclusively identified in AdCC and 106 in PAc. Clustering analysis of the statistically significant proteins clearly separated AdCC from PAc. Protein expression 10 times higher in one group than in the other led to a signature of 16 proteins-6 upregulated in AdCC and 10 in PAc. A new clustering analysis showed reverse regulation and also differentiated both tumors. CONCLUSIONS: Global proteomics may be useful in discriminating these two malignant salivary neoplasms that frequently show clinical and microscopic overlaps, but additional validation studies are still necessary to determine the diagnostic potential of the protein signature obtained.
OBJECTIVE: The aim of this study was to determine the proteome of adenoid cystic carcinoma (AdCC) and polymorphous adenocarcinoma (PAc) and to identify a protein signature useful in distinguishing these two neoplasms. STUDY DESIGN: Ten cases of AdCC and 10 cases of PAc were microdissected for enrichment of neoplastic tissue. The samples were submitted to liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the proteomics data were analyzed by using the MaxQuant software. LC-MS/MS spectra were searched against the Human UniProt database, and statistical analyses were performed with Perseus software. Bioinformatic analyses were performed by using discovery-based proteomic data on both tumors. RESULTS: LC-MS/MS analysis identified 1957 proteins. The tumors shared 1590 proteins, and 261 were exclusively identified in AdCC and 106 in PAc. Clustering analysis of the statistically significant proteins clearly separated AdCC from PAc. Protein expression 10 times higher in one group than in the other led to a signature of 16 proteins-6 upregulated in AdCC and 10 in PAc. A new clustering analysis showed reverse regulation and also differentiated both tumors. CONCLUSIONS: Global proteomics may be useful in discriminating these two malignant salivary neoplasms that frequently show clinical and microscopic overlaps, but additional validation studies are still necessary to determine the diagnostic potential of the protein signature obtained.