Role of gene signatures combined with pathology in classification of oropharynx head and neck cancer.
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
/ genetics
Carcinoma, Squamous Cell
/ classification
Combined Modality Therapy
Female
Follow-Up Studies
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Male
Middle Aged
Oropharyngeal Neoplasms
/ classification
Prognosis
Retrospective Studies
Survival Rate
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
23 06 2020
23 06 2020
Historique:
received:
14
10
2019
accepted:
01
06
2020
entrez:
25
6
2020
pubmed:
25
6
2020
medline:
15
12
2020
Statut:
epublish
Résumé
Treatment personalisation remains an unmet need in oropharynx cancer (OPC). We aimed to determine whether gene expression signatures improved upon clinico-pathological predictors of outcome in OPC. The clinico-pathological predictors, AJCC version 7 (AJCC 7), AJCC 8, and a clinical algorithm, were assessed in 4 public series of OPC (n = 235). Literature review identified 16 mRNA gene expression signatures of radiosensitivity, HPV status, tumour hypoxia, and microsatellite instability. We quality tested signatures using a novel sigQC methodology, and added signatures to clinico-pathological variables as predictors of survival, in univariate and multivariate analyses. AJCC 7 Stage was not predictive of recurrence-free survival (RFS) or overall survival (OS). AJCC 8 significantly predicted RFS and OS. Gene signature quality was highly variable. Among HPV-positive cases, signatures for radiosensitivity, hypoxia, and microsatellite instability revealed significant underlying inter-tumour biological heterogeneity, but did not show prognostic significance when adjusted for clinical covariates. Surprisingly, among HPV-negative cases, a gene signature for HPV status was predictive of survival, even after adjustment for clinical covariates. Across the whole series, several gene signatures representing HPV and microsatellite instability remained significant in multivariate analysis. However, quality control and independent validation remain to be performed to add prognostic information above recently improved clinico-pathological variables.
Identifiants
pubmed: 32576885
doi: 10.1038/s41598-020-66983-x
pii: 10.1038/s41598-020-66983-x
pmc: PMC7311543
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
10226Subventions
Organisme : Cancer Research UK
Pays : United Kingdom
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