Abstract
BackgroundHuman head and neck squamous cell carcinoma (HNSCC) is an aggressive and recurrent malignancy. Identification of unique or overexpressed cell-associated or cell surface antigens is critical for diagnosis and development of cancer vaccines and targeted therapies for HNSCC. We have used high throughput microarray technology to search for candidate targets in HNSCC.MethodsGene expression profiling in 17 HNSCC tumors and 3 normal tonsil tissues was performed by microarray. QRT-PCR analysis was performed to validate the microarray results. The five candidate genes were further characterized by immunohistochemical technique in surgical samples and tissue arrays.ResultsA total of 192 up-regulated genes at statistical significance of p < 0.01 and log2 ratio ≥ 1 were identified in HNSCC tumors compared to normal tissues. These genes belong to immune response, cell growth, cell cycle regulation, oncogenes, metabolism and others. Five potential novel target genes (FABP5, CD24, CD44, CD74, and HSP27) were identified, which were highly expressed in HNSCC tumor samples and tissue arrays. CD24, CD44, and CD74 proteins were expressed on the cell surface, and FABP5 and HSP27 proteins were predominantly expressed in the cytoplasm of HNSCC.ConclusionFive genes and their products may serve as a diagnostic biomarker or therapeutic target for HNSCC. While additional work is needed to elucidate the biological significance of these proteins, CD24 and CD74 expressed only in small proportion of cells indicating tumor heterogeneity and subtypes of tumor initiating cells (CD24+/CD44+) present in HNSCC.
Highlights
Human head and neck squamous cell carcinoma (HNSCC) is an aggressive and recurrent malignancy
In order to identify the potential therapeutic targets in HNSCC, we mainly focused on the up-regulated genes in HNSCC
Expression of Selected Gene Products in HNSCC To narrow down the range of potential therapeutic targets in 192 up-regulated genes identified in our HNSCC samples, we mainly focused on the genes encoding cell surface receptors and some cytoplasmic proteins
Summary
Human head and neck squamous cell carcinoma (HNSCC) is an aggressive and recurrent malignancy. Identification of unique or overexpressed cell-associated or cell surface antigens is critical for diagnosis and development of cancer vaccines and targeted therapies for HNSCC. More than 90% of head and neck cancers are of squamous cell carcinoma, and arise from diverse anatomical locations, including lip/oral cavity, nasopharynx, oropharynx, lar-. The survival rate of patients with head & neck squamous cell carcinoma (HNSCC) has not improved significantly despite multimodality therapy including surgery, radiation therapy, and chemotherapy. Recent investigations have focused on novel therapeutic approaches, and on the identification of molecular targets for therapy [3,4]. Identification of unique or overexpressed antigens or cell surface proteins is critical for the development of cancer vaccines and targeted immunotoxins or cytotoxins, which may offer alternative approach for caner therapy
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