Expanding the Transcriptome of Head and Neck Squamous Cell Carcinoma Through Novel MicroRNA Discovery

Autor(es)

Rock, Leigha D. ^{[1, 2, 3, 4]} ; Minatel, Brenda C. ^[1] ; Marshall, Erin A. ^[1] ; Guisier, Florian ^{[1, 5, 6]} ; Sage, Adam P. ^[1] ; Barros-Filho, Mateus Camargo ^{[7, 1]} ; Stewart, Greg L. ^[1] ; Garnis, Cathie ^[1] ; Lam, Wan L. ^[1]

Afiliação do(s) autor(es)

^[1] British Columbia Canc Res Ctr, Dept Integrat Oncol, Vancouver, BC - Canada

^[2] British Columbia Canc Res Ctr, Dept Canc Control Res, Vancouver, BC - Canada

^[3] Univ British Columbia, Fac Dent, Vancouver, BC - Canada

^[4] Dalhousie Univ, Fac Dent, Halifax, NS - Canada

^[5] Rouen Univ Hosp, Dept Pulmonol, Rouen - France

^[6] Rouen Univ Hosp, CIC CRB 1404, Rouen - France

^[7] AC Camargo Canc Ctr, Int Res Ctr, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN ONCOLOGY; v. 9, NOV 27 2019.
• Citações Web of Science: 0

Resumo

Head and neck squamous cell carcinoma (HNSCC) has a poor survival rate mainly due to late stage diagnosis and recurrence. Despite genomic efforts to identify driver mutations and changes in protein-coding gene expression, developing effective diagnostic and prognostic biomarkers remains a priority to guide disease management and improve patient outcome. Recent reports of previously-unannotated microRNAs (miRNAs) from multiple somatic tissues have raised the possibility of HNSCC-specific miRNAs. In this study, we applied a customized in-silico analysis pipeline to identify novel miRNAs from raw small-RNA sequencing datasets from public repositories. We discovered 146 previously-unannotated sequences expressed in head and neck samples that share structural properties highly characteristic of miRNAs. The combined expression of the novel miRNAs revealed tissue and context-specific patterns. Furthermore, comparison of tumor with non-malignant tissue samples (n = 43 pairs) revealed 135 of these miRNAs as differentially expressed, most of which were overexpressed or exclusively found in tumor samples. Additionally, a subset of novel miRNAs was significantly associated with HPV infection status and patient outcome. A prognostic-model combining novel and known miRNA was developed (multivariate Cox regression analysis) leading to an improved death and relapse risk stratification (log rank p < 1e-7). The presence of these miRNAs was corroborated both in an independent dataset and by RT-qPCR analysis, supporting their potential involvement in HNSCC. In this study, we report the discovery of 146 novel miRNAs in head and neck tissues and demonstrate their potential biological significance and clinical relevance to head and neck cancer, providing a new resource for the study of HNSCC. (AU)

• Processo FAPESP: 18/06138-8 - Pequenos RNAs não codificadores como reguladores chave no câncer de tireóide
• Beneficiário: Mateus de Camargo Barros Filho
• Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado