Functional microarray analysis suggests repressed cell-cell signaling and cell survival-related modules inhibit progression of head and neck squamous cell carcinoma

Autor(es)

Colo, Anna E. L. ^{[1, 2]} ; Simoes, Ana C. Q. ^[3] ; Carvalho, Andre L. ^[2] ; Melo, Camila M. ^[2] ; Fahham, Lucas ^[4] ; Kowalski, Luiz P. ^[2] ; Soares, Fernando A. ^[2] ; Neves, Eduardo J. ^[4] ; Reis, Luiz F. L. ^{[2, 5]} ; Carvalho, Alex F. ^[2]

Afiliação do(s) autor(es)

^[1] Hosp Israelita Albert Einstein, BR-05652900 Sao Paulo - Brazil

^[2] Hosp AC Camargo Fund Antonio Prudente, BR-01508010 Sao Paulo - Brazil

^[3] Univ Fed ABC, BR-09210170 Santo Andre, SP - Brazil

^[4] Univ Sao Paulo, Inst Matemat & Estat, BR-05508090 Sao Paulo - Brazil

^[5] Hosp Sirio Libanes, BR-01308050 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BMC MEDICAL GENOMICS; v. 4, APR 13 2011.
• Citações Web of Science: 3

Resumo

Background: Cancer shows a great diversity in its clinical behavior which cannot be easily predicted using the currently available clinical or pathological markers. The identification of pathways associated with lymph node metastasis (N+) and recurrent head and neck squamous cell carcinoma (HNSCC) may increase our understanding of the complex biology of this disease. Methods: Tumor samples were obtained from untreated HNSCC patients undergoing surgery. Patients were classified according to pathologic lymph node status (positive or negative) or tumor recurrence (recurrent or non-recurrent tumor) after treatment (surgery with neck dissection followed by radiotherapy). Using microarray gene expression, we screened tumor samples according to modules comprised by genes in the same pathway or functional category. Results: The most frequent alterations were the repression of modules in negative lymph node (N0) and in non-recurrent tumors rather than induction of modules in N+ or in recurrent tumors. N0 tumors showed repression of modules that contain cell survival genes and in non-recurrent tumors cell-cell signaling and extracellular region modules were repressed. Conclusions: The repression of modules that contain cell survival genes in N0 tumors reinforces the important role that apoptosis plays in the regulation of metastasis. In addition, because tumor samples used here were not microdissected, tumor gene expression data are represented together with the stroma, which may reveal signaling between the microenvironment and tumor cells. For instance, in non-recurrent tumors, extracellular region module was repressed, indicating that the stroma and tumor cells may have fewer interactions, which disable metastasis development. Finally, the genes highlighted in our analysis can be implicated in more than one pathway or characteristic, suggesting that therapeutic approaches to prevent tumor progression should target more than one gene or pathway, specially apoptosis and interactions between tumor cells and the stroma. (AU)

• Processo FAPESP: 98/14335-2 - Antonio Prudente Cancer Research Center
• Beneficiário: Fernando Augusto Soares
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs