Gene expression signatures and molecular markers associated with clinical outcome in locally advanced head and neck carcinoma

被引:31
作者
Pavon, M. A. [1 ,2 ]
Parreno, M. [1 ,2 ,7 ]
Tellez-Gabriel, M. [1 ,2 ]
Sancho, F. J. [2 ,3 ]
Lopez, M.
Cespedes, M., V [1 ,2 ]
Casanova, I [1 ,2 ]
Lopez-Pousa, A. [4 ]
Mangues, M. A. [5 ]
Quer, M. [6 ]
Barnadas, A. [4 ]
Leon, X. [2 ,6 ]
Mangues, R. [1 ]
机构
[1] IIB Sant Pau, GOA, Barcelona, Spain
[2] CIBER Bioingn Biomat Nanomed CIBER BBN, Barcelona, Spain
[3] Hosp Santa Creu & Sant Pau, Dept Pathol, IIB Sant Pau, Barcelona, Spain
[4] Hosp Santa Creu & Sant Pau, Dept Med Oncol, IIB Sant Pau, Barcelona, Spain
[5] Hosp Santa Creu & Sant Pau, Dept Pharm, IIB Sant Pau, Barcelona, Spain
[6] Hosp Santa Creu & Sant Pau, Dept Otorhinolaryngol ORL, IIB Sant Pau, Barcelona, Spain
[7] IIB Sant Pau, Translat Mol Oncol, Barcelona, Spain
关键词
SQUAMOUS-CELL CARCINOMA; NF-KAPPA-B; MALIGNANT PHENOTYPE; POOR-PROGNOSIS; BREAST-CANCER; LUNG-CANCER; ACTIVATION; PROFILES; BIOLOGY; TUMOR;
D O I
10.1093/carcin/bgs207
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The purpose of this study was to identify molecular markers associated with tumor recurrence and survival in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). We studied the expression profile of 63 pre-treatment tumor biopsies obtained from locally advanced HNSCCs treated with standard treatments. Cluster analysis identified three tumor subtypes associated with significant differences in local recurrence-free survival (LRFS) (P < 0.001), progression free-survival (PFS) (P < 0.009) and overall survival (OS) (P < 0.004). Tumor subtype 1, associated with short LRFS, PFS and OS, showed features of epithelialmesenchymal transition and undifferentiation. It also overexpressed genes involved in cell adhesion, NF-B and integrin signalling. Tumor subtype 3, associated with longer LRFS, PFS and OS, showed a high degree of differentiation and overexpressed genes located in chromosomal regions 19q13 and 1q21. Tumor subtype 2, which had an intermediate clinical outcome between subtype 1 and subtype 3, overexpressed genes involved in branching morphogenesis. Finally, we validated the association between gene cluster classification and patient survival using Gene Set Enrichment Analysis and two HNSCC data sets obtained from two independent patient cohorts. In conclusion, we generated a gene prognostic signature associated with survival in locally advanced patients using the expression profile of the pre-treatment tumor biopsy. Independent prospective studies would be necessary to assess if the proposed survival signature could help to guide clinical management of HNSCC.
引用
收藏
页码:1707 / 1716
页数:10
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