Análise integrada entre dados de expressão global de transcritos codificadores e de miRNAs em carcinomas de células escamosas de laringe

• Ano de defesa: 2015
• Autor(a) principal: Lapa, Rainer Marco Lopez [UNESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Estadual Paulista (Unesp)
• Palavras-chave em Português: Carcinoma de células escamosas; Expressão gênica; Microarranjos de DNA; Virus do papiloma; Laringe - Câncer; DNA microarrays; Carcinoma, Squamous Cell
• Link de acesso: http://hdl.handle.net/11449/134088; http://www.athena.biblioteca.unesp.br/exlibris/bd/cathedra/14-01-2016/000854236.pdf

Laryngeal squamous cell carcinoma (LSCC) is one of the most common head and neck malignancies representing approximately 25% of the tumors located in this region. Risk factors associated to development of LSCCs include alcohol and tobacco consumption, family history of cancer and human papilloma virus (HPV) infection. Second primary tumors and metastasis are frequently observed in patients with LSCC. To date, no useful molecular markers have been described that can successfully predict disease progression and clinical outcome. In this context, large scale molecular studies enable a global analysis of tumor molecular alterations aiming to reveal biomarkers for early diagnosis, prognosis and response to therapy. LSCC samples were obtained from 88 untreated patients. Global gene (Array plataform 8x60K, Agilent Technologies) and miRNA expression (Array platform 8x60K, Agilent Technologies) profiles were evaluated in 35 and 33 samples, respectively (Test group, N=36). An independent group of samples (N=33, validation group) was included, being 33 formalin fixed and paraffin embedded tissue samples and 19 fresh frozen tissues. HPV genotyping using LINEAR ARRAY HPV Genotyping Test (Roche) was performed in tumor samples from test group. Only two cases were HPV16-positive. The expression analysis revealed 1,680 differentially expressed genes in tumors compared to normal tissue (pool of normal laryngeal samples from necropsies). The miRNA analysis revealed 89 miRNAs differentially expressed. Integrative transcriptome and miRNAs analysis data (negative correlation r<0) revealed a subset of altered genes associated with the degradation of extracellular matrix components (MMP3, MMP9, MMP10, MMP13, COL10A1 and COL3A1) and neoplastic processes (CAV1, ERBB4, HLF,HMGA2, HOXB6, KLF2, PDCD4, PPP1R3 and TOP2), as well as their putative miRNA regulators (hsa-miR-199b-5p, hsa-miR-218-5p, hsa-miR-29c-3p, hsa-miR-21-5p, hsa-miR-204-5p, hsa-miR-125b-5p, hsa-miR- ...