Searching for molecular markers in head and neck squamous cell carcinomas (HNSCC) by statistical and bioinformatic analysis of larynx-derived SAGE libraries

Author(s):Show less -

Silveira, Nelson J. F. ^[1] ; Varuzza, Leonardo ^[2] ; Machado-Lima, Ariane ^[3] ; Lauretto, Marcelo S. ^[2] ; Pinheiro, Daniel G. ^[4] ; Rodrigues, Rodrigo V. ^{[5, 6]} ; Severino, Patricia ^[7] ; Nobrega, Francisco G. ^[8] ; Silva, Jr., Wilson A. ^[4] ; Pereira, Carlos A. de B. ^[2] ; Tajara, Eloiza H. ^{[5, 6]} ; GENCAPO, Head Neck Genome Project

Affiliation

^[1] UNIVAP, Inst Pesquisa & Desenvolvimento, Sao Jose Dos Campos, SP - Brazil

^[2] Univ Sao Paulo, Inst Matemat & Estatist, BR-09500900 Sao Paulo - Brazil

^[3] Univ Sao Paulo, BIOINFO USP Nucleo Pesquisas Bioinformat, BR-09500900 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Fac Med Ribeirao Preto, Ctr Reg Hemoterapia, Ctr Terapia Celular, Dept Genet, BR-09500900 Sao Paulo - Brazil

^[5] Univ Sao Paulo, Inst Biociencias, Dept Genet & Biol Evolut, BR-09500900 Sao Paulo - Brazil

^[6] FAMERP, Fac Med Sao Jose Rio Preto, Dept Biol Mol, Sao Jose Do Rio Preto, SP - Brazil

^[7] Inst Ensino & Pesquisa Albert Einstein, Sao Paulo - Brazil

^[8] UNESP, Fac Odontol, Dept Biociencias & Diagnost Bucal, Sao Jose Dos Campos - Brazil

• Document type: Journal article
• Source: BMC MEDICAL GENOMICS; v. 1, NOV 11 2008.
• Web of Science Citations: 24

Abstract

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies in humans. The average 5-year survival rate is one of the lowest among aggressive cancers, showing no significant improvement in recent years. When detected early, HNSCC has a good prognosis, but most patients present metastatic disease at the time of diagnosis, which significantly reduces survival rate. Despite extensive research, no molecular markers are currently available for diagnostic or prognostic purposes. Methods: Aiming to identify differentially-expressed genes involved in laryngeal squamous cell carcinoma (LSCC) development and progression, we generated individual Serial Analysis of Gene Expression (SAGE) libraries from a metastatic and non-metastatic larynx carcinoma, as well as from a normal larynx mucosa sample. Approximately 54,000 unique tags were sequenced in three libraries. Results: Statistical data analysis identified a subset of 1,216 differentially expressed tags between tumor and normal libraries, and 894 differentially expressed tags between metastatic and non-metastatic carcinomas. Three genes displaying differential regulation, one down-regulated (KRT31) and two up-regulated (BST2, MFAP2), as well as one with a non-significant differential expression pattern (GNA15) in our SAGE data were selected for real-time polymerase chain reaction (PCR) in a set of HNSCC samples. Consistent with our statistical analysis, quantitative PCR confirmed the upregulation of BST2 and MFAP2 and the downregulation of KRT31 when samples of HNSCC were compared to tumor-free surgical margins. As expected, GNA15 presented a non-significant differential expression pattern when tumor samples were compared to normal tissues. Conclusion: To the best of our knowledge, this is the first study reporting SAGE data in head and neck squamous cell tumors. Statistical analysis was effective in identifying differentially expressed genes reportedly involved in cancer development. The differential expression of a subset of genes was confirmed in additional larynx carcinoma samples and in carcinomas from a distinct head and neck subsite. This result suggests the existence of potential common biomarkers for prognosis and targeted-therapy development in this heterogeneous type of tumor. (AU)

• FAPESP's process: 04/12054-9 - Markers of aggressive behavior in head and neck tumors
• Grantee: Eloiza Helena Tajara da Silva
• Support Opportunities: Research Projects - Thematic Grants