Gene expression signatures and molecular markers predict response to therapy in locally advanced head and neck squamous cell carcinoma.

ABSTRACT: Locally advanced head and neck squamous cell carcinomas (HNSCC) are commonly treated with chemoradiotherapy (CRT) or induction chemotherapy followed by radiotherapy/CRT or surgery. The purpose of our study was to identify expression signatures and molecular markers able to anticipate tumor response to therapy and clinical outcome. We performed a study with 63 pre-treatment tumor biopsies from locally advanced HNSCC treated with either of the two standard treatments. Cluster analysis identified three tumor subtypes associated with significant differences in local recurrence-free survival (LRFS) and overall survival (OS). Tumor subtype 1, associated with low LRFS and OS, showed features of epithelial-mesenchymal transition and undifferentiation. It also overexpressed genes related to cell adhesion, NF-κB and integrin signalling pathways. Tumor subtype 3, associated with a high LRFS and OS, showed a high degree of differentiation and overexpressed genes located in chromosome regions 19q13 and 1q21. Tumor subtype 2, with a LRFS that was similar to subtype 3 and an OS similar to subtype 1, overexpressed genes involved in branching morphogenesis. ROC analysis identified genes associated with local recurrence and survival. Using qRT-PCR we confirmed the association of RAB25, DUOX1 and THBS1 expression with LRFS and OS. Patients whose tumors displayed high RAB25 or DUOX1 mRNA levels had longer LRFS and OS than patients with low mRNA levels. In contrast, patients bearing tumors with high THBS1 levels had a shorter OS than patients with low THBS1 levels. RAB25, DUOX1 and THBS1 could be good molecular markers to identify patients who would benefit from genotoxic treatment. Sixty three pretreatment HNSCC biopsies and five normal mucosas were assayed using the Affymetrix HG-U133A2.0 array.

ORGANISM(S): Homo sapiens

SUBMITTER: MIGUEL ANGEL PAVON 

PROVIDER: E-GEOD-23036 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress