Predictive biomarkers in oropharynx squamous cell carcinoma

• Grant number: 11/11085-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2012
• End date: December 31, 2013
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Silvia Regina Rogatto
• Grantee: Marcia Hatakeyama
• Host Institution: A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil
• Associated research grant: 08/57887-9 - National Institute of Oncogenomics, AP.TEM

Abstract

There are few reports in literature that associate biological predictors of response to radiotherapy and/or chemotherapy in oropharyngeal SCC, and most of them are based on heterogeneous groups of tumors localized in the upper aerodigestive tract. In a previous study of the group from a total of 37 samples of oropharynx SCC, 32 cases were evaluated by CGH array (4x180k, Agilent). The array CGH analysis demonstrated significant genomic alterations involving chromosomes 3, 8, 2 and 1 (216, 208, 204 and 199 CNAs, respectively). Thirty-five percent were positive for HPV infection, and subtype HPV16 was the most prevalent (8 / 37). HPV-negative cases showed a large number of CNAs (117 CNAs), while the majority of HPV-positive patients had a genomic profile with less number of genomic alterations (73 CNAs). Changes in regions 7q22.1 (12 genes) and 14q12 (2 genes) were lost only in HPV-positive tumors (p=0.044). Alterations found on chromosomes 1, 9, 10 and 19 were frequently detected in tumors that showed partial response or progressive disease (PD). The regions of losses on 1p21.3-p21.2, 1p21.2-p21.1 and 1p21.1 and gains on 10p13-p12.33, 10p12.31-p12.1 were only altered in cases that do not showed CR (complete response) (pd0.017). There was not a significant difference in OS between HPV- and HPV+ cases (p>0.05). However, there was a significant relationship between CR patients and PD (p=0.018). The global assessment of gene expression revealed 1.937 differentially expressed genes, being 956 (49.4%) with increased and 981 (50.6%) with decreased expression. A supervised clustering analysis regarding the pattern of HPV infection (9 positive cases vs 13 negative cases), revealed 104 genes differentially expressed between the two groups, being 58 genes with increased expression and 46 with decreased expression in HPV+ tumors compared to HPV-. The aim of this study is to investigate biological markers that could act as potential predictors of response to chemotherapy and/or radiotherapy according to HPV infection, validate and verify alterations in candidate genes that may serve as potential predictors of treatment response in 45 oropharynx carcinomas under the same treatment protocol. This study is a sequence of other study in the same group using integrated analysis (genomics and transcriptomics) according to the pattern of HPV infection with the same treatment protocol showing several candidate markers of response to therapy.