Expanding the Transcriptome of Head and Neck Squamous Cell Carcinoma Through Novel MicroRNA Discovery
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 t...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-11-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2019.01305/full |
| _version_ | 1819125430095970304 |
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| author | Leigha D. Rock Leigha D. Rock Leigha D. Rock Leigha D. Rock Brenda C. Minatel Erin A. Marshall Florian Guisier Florian Guisier Adam P. Sage Mateus Camargo Barros-Filho Mateus Camargo Barros-Filho Greg L. Stewart Cathie Garnis Wan L. Lam |
| author_facet | Leigha D. Rock Leigha D. Rock Leigha D. Rock Leigha D. Rock Brenda C. Minatel Erin A. Marshall Florian Guisier Florian Guisier Adam P. Sage Mateus Camargo Barros-Filho Mateus Camargo Barros-Filho Greg L. Stewart Cathie Garnis Wan L. Lam |
| author_sort | Leigha D. Rock |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T07:40:00Z |
| format | Article |
| id | doaj.art-fa5fdcfaec9e46ec814413c38c2d175d |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-22T07:40:00Z |
| publishDate | 2019-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-fa5fdcfaec9e46ec814413c38c2d175d2022-12-21T18:33:47ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-11-01910.3389/fonc.2019.01305484432Expanding the Transcriptome of Head and Neck Squamous Cell Carcinoma Through Novel MicroRNA DiscoveryLeigha D. Rock0Leigha D. Rock1Leigha D. Rock2Leigha D. Rock3Brenda C. Minatel4Erin A. Marshall5Florian Guisier6Florian Guisier7Adam P. Sage8Mateus Camargo Barros-Filho9Mateus Camargo Barros-Filho10Greg L. Stewart11Cathie Garnis12Wan L. Lam13Department of Cancer Control Research, British Columbia Cancer Research Centre, Vancouver, BC, CanadaFaculty of Dentistry, University of British Columbia, Vancouver, BC, CanadaDepartment of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, BC, CanadaFaculty of Dentistry, Dalhousie University, Halifax, NS, CanadaDepartment of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, BC, CanadaDepartment of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, BC, CanadaDepartment of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, BC, CanadaDepartment of Pulmonology and CIC-CRB 1404, Rouen University Hospital, Rouen, FranceDepartment of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, BC, CanadaDepartment of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, BC, CanadaInternational Research Center—A.C.Camargo Cancer Center, São Paulo, BrazilDepartment of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, BC, CanadaDepartment of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, BC, CanadaDepartment of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, BC, CanadaHead 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.https://www.frontiersin.org/article/10.3389/fonc.2019.01305/fullmicroRNAsnon-coding RNAgene expression profilinghead and neck cancercomputational biology |
| spellingShingle | Leigha D. Rock Leigha D. Rock Leigha D. Rock Leigha D. Rock Brenda C. Minatel Erin A. Marshall Florian Guisier Florian Guisier Adam P. Sage Mateus Camargo Barros-Filho Mateus Camargo Barros-Filho Greg L. Stewart Cathie Garnis Wan L. Lam Expanding the Transcriptome of Head and Neck Squamous Cell Carcinoma Through Novel MicroRNA Discovery Frontiers in Oncology microRNAs non-coding RNA gene expression profiling head and neck cancer computational biology |
| title | Expanding the Transcriptome of Head and Neck Squamous Cell Carcinoma Through Novel MicroRNA Discovery |
| title_full | Expanding the Transcriptome of Head and Neck Squamous Cell Carcinoma Through Novel MicroRNA Discovery |
| title_fullStr | Expanding the Transcriptome of Head and Neck Squamous Cell Carcinoma Through Novel MicroRNA Discovery |
| title_full_unstemmed | Expanding the Transcriptome of Head and Neck Squamous Cell Carcinoma Through Novel MicroRNA Discovery |
| title_short | Expanding the Transcriptome of Head and Neck Squamous Cell Carcinoma Through Novel MicroRNA Discovery |
| title_sort | expanding the transcriptome of head and neck squamous cell carcinoma through novel microrna discovery |
| topic | microRNAs non-coding RNA gene expression profiling head and neck cancer computational biology |
| url | https://www.frontiersin.org/article/10.3389/fonc.2019.01305/full |
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