Abstract
BackgroundHead and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies in humans. The average 5-year survival rate is one of the lowest among aggressive cancers, showing no significant improvement in recent years. When detected early, HNSCC has a good prognosis, but most patients present metastatic disease at the time of diagnosis, which significantly reduces survival rate. Despite extensive research, no molecular markers are currently available for diagnostic or prognostic purposes.MethodsAiming to identify differentially-expressed genes involved in laryngeal squamous cell carcinoma (LSCC) development and progression, we generated individual Serial Analysis of Gene Expression (SAGE) libraries from a metastatic and non-metastatic larynx carcinoma, as well as from a normal larynx mucosa sample. Approximately 54,000 unique tags were sequenced in three libraries.ResultsStatistical data analysis identified a subset of 1,216 differentially expressed tags between tumor and normal libraries, and 894 differentially expressed tags between metastatic and non-metastatic carcinomas. Three genes displaying differential regulation, one down-regulated (KRT31) and two up-regulated (BST2, MFAP2), as well as one with a non-significant differential expression pattern (GNA15) in our SAGE data were selected for real-time polymerase chain reaction (PCR) in a set of HNSCC samples. Consistent with our statistical analysis, quantitative PCR confirmed the upregulation of BST2 and MFAP2 and the downregulation of KRT31 when samples of HNSCC were compared to tumor-free surgical margins. As expected, GNA15 presented a non-significant differential expression pattern when tumor samples were compared to normal tissues.ConclusionTo the best of our knowledge, this is the first study reporting SAGE data in head and neck squamous cell tumors. Statistical analysis was effective in identifying differentially expressed genes reportedly involved in cancer development. The differential expression of a subset of genes was confirmed in additional larynx carcinoma samples and in carcinomas from a distinct head and neck subsite. This result suggests the existence of potential common biomarkers for prognosis and targeted-therapy development in this heterogeneous type of tumor.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies in humans
Statistical analysis of Serial Analysis of Gene Expression (SAGE) data We constructed three SAGE libraries from two larynx carcinoma samples and a pooled control sample aiming to identify global events involved in tumorigenesis and potential biomarkers in HNSCC
Given the huge amount of data generated by SAGE, events that play a consistent role in cancer phenotype may be undistinguished from those that are random events, leading to false positive and false negative results
Summary
Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies in humans. HNSCC has a good prognosis, but most patients present metastatic disease at the time of diagnosis, which significantly reduces survival rate. In Brazil, over 13,000 new cases are expected in 2008 [2] Advances in both surgical and nonsurgical therapeutics have led to increased local tumor control. HNSCC has a 75% 5-year survival rate, but most patients present metastatic disease at the time of diagnosis, which reduces survival rate to 35% [4]. This 5-year survival rate is one of the lowest among aggressive cancers and has shown no significant improvement in recent years [5,6]
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