Spectral clustering of microarray data elucidates the roles of microenvironment remodeling and immune responses in survival of head and neck squamous cell carcinoma.

2.50
Hdl Handle:
http://hdl.handle.net/10541/109051
Title:
Spectral clustering of microarray data elucidates the roles of microenvironment remodeling and immune responses in survival of head and neck squamous cell carcinoma.
Authors:
Thurlow, Johanna K; Peña Murillo, Claudia L; Hunter, Keith; Buffa, Francesca M; Patiar, Shalini; Betts, Guy N J; West, Catharine M L; Harris, Adrian L; Parkinson, Eric K; Harrison, Paul R; Ozanne, Bradford W; Partridge, Max; Kalna, Gabriela
Abstract:
PURPOSE: To identify functionally related prognostic gene sets for head and neck squamous cell carcinoma (HNSCC) by unsupervised statistical analysis of microarray data. PATIENTS AND METHODS: Microarray analysis was performed on 14 normal oral epithelium and 71 HNSCCs from patients with outcome data. Spectral clustering (SC) analysis of the data set identified multiple vectors representing distinct aspects of gene expression heterogeneity between samples. Gene ontology (GO) analysis of vector gene lists identified gene sets significantly enriched within defined biologic pathways. The prognostic significance of these was established by Cox survival analysis. RESULTS: The most influential SC vectors were V2 and V3. V2 separated normal from tumor samples. GO analysis of V2 gene lists identified pathways with heterogeneous expression between HNSCCs, notably focal adhesion (FA)/extracellular matrix remodeling and cytokine-cytokine receptor (CR) interactions. Similar analysis of V3 gene lists identified further heterogeneity in CR pathways. V2CR genes represent an innate immune response, whereas high expression of V3CR genes represented an adaptive immune response that was not dependent on human papillomavirus status. Survival analysis demonstrated that the FA gene set was prognostic of poor outcome, whereas classification for adaptive immune response by the CR gene set was prognostic of good outcome. A combined FA&CR model dramatically exceeded the performance of current clinical classifiers (P < .001 in our cohort and, importantly, P = .007 in an independent cohort of 60 HNSCCs). CONCLUSION: The application of SC and GO algorithms to HNSCC microarray data identified gene sets highly significant for predicting patient outcome. Further large-scale studies will establish the usefulness of these gene sets in the clinical management of HNSCC.
Affiliation:
The Beatson Institute for Cancer Research, Glasgow, Scotland, United Kingdom.
Citation:
Spectral clustering of microarray data elucidates the roles of microenvironment remodeling and immune responses in survival of head and neck squamous cell carcinoma. 2010, 28 (17):2881-8 J Clin Oncol
Journal:
Journal of Clinical Oncology
Issue Date:
10-Jun-2010
URI:
http://hdl.handle.net/10541/109051
DOI:
10.1200/JCO.2009.24.8724
PubMed ID:
20458058
Type:
Article
Language:
en
ISSN:
1527-7755
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorThurlow, Johanna Ken
dc.contributor.authorPeña Murillo, Claudia Len
dc.contributor.authorHunter, Keithen
dc.contributor.authorBuffa, Francesca Men
dc.contributor.authorPatiar, Shalinien
dc.contributor.authorBetts, Guy N Jen
dc.contributor.authorWest, Catharine M Len
dc.contributor.authorHarris, Adrian Len
dc.contributor.authorParkinson, Eric Ken
dc.contributor.authorHarrison, Paul Ren
dc.contributor.authorOzanne, Bradford Wen
dc.contributor.authorPartridge, Maxen
dc.contributor.authorKalna, Gabrielaen
dc.date.accessioned2010-08-04T13:19:22Z-
dc.date.available2010-08-04T13:19:22Z-
dc.date.issued2010-06-10-
dc.identifier.citationSpectral clustering of microarray data elucidates the roles of microenvironment remodeling and immune responses in survival of head and neck squamous cell carcinoma. 2010, 28 (17):2881-8 J Clin Oncolen
dc.identifier.issn1527-7755-
dc.identifier.pmid20458058-
dc.identifier.doi10.1200/JCO.2009.24.8724-
dc.identifier.urihttp://hdl.handle.net/10541/109051-
dc.description.abstractPURPOSE: To identify functionally related prognostic gene sets for head and neck squamous cell carcinoma (HNSCC) by unsupervised statistical analysis of microarray data. PATIENTS AND METHODS: Microarray analysis was performed on 14 normal oral epithelium and 71 HNSCCs from patients with outcome data. Spectral clustering (SC) analysis of the data set identified multiple vectors representing distinct aspects of gene expression heterogeneity between samples. Gene ontology (GO) analysis of vector gene lists identified gene sets significantly enriched within defined biologic pathways. The prognostic significance of these was established by Cox survival analysis. RESULTS: The most influential SC vectors were V2 and V3. V2 separated normal from tumor samples. GO analysis of V2 gene lists identified pathways with heterogeneous expression between HNSCCs, notably focal adhesion (FA)/extracellular matrix remodeling and cytokine-cytokine receptor (CR) interactions. Similar analysis of V3 gene lists identified further heterogeneity in CR pathways. V2CR genes represent an innate immune response, whereas high expression of V3CR genes represented an adaptive immune response that was not dependent on human papillomavirus status. Survival analysis demonstrated that the FA gene set was prognostic of poor outcome, whereas classification for adaptive immune response by the CR gene set was prognostic of good outcome. A combined FA&CR model dramatically exceeded the performance of current clinical classifiers (P < .001 in our cohort and, importantly, P = .007 in an independent cohort of 60 HNSCCs). CONCLUSION: The application of SC and GO algorithms to HNSCC microarray data identified gene sets highly significant for predicting patient outcome. Further large-scale studies will establish the usefulness of these gene sets in the clinical management of HNSCC.en
dc.language.isoenen
dc.subjectHead and Neck Squamous Cell Carcinomaen
dc.subjectMicroarray Dataen
dc.subjectMicroarray Analysisen
dc.subjectSpectral Clustering Analysisen
dc.subjectGene Setsen
dc.subject.meshCarcinoma, Squamous Cell-
dc.subject.meshCytokines-
dc.subject.meshGene Expression Regulation, Neoplastic-
dc.subject.meshHead and Neck Neoplasms-
dc.subject.meshOligonucleotide Array Sequence Analysis-
dc.titleSpectral clustering of microarray data elucidates the roles of microenvironment remodeling and immune responses in survival of head and neck squamous cell carcinoma.en
dc.typeArticleen
dc.contributor.departmentThe Beatson Institute for Cancer Research, Glasgow, Scotland, United Kingdom.en
dc.identifier.journalJournal of Clinical Oncologyen

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