Identification of potential therapeutic targets in human head & neck squamous cell carcinoma.
BACKGROUND
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. We have used high throughput microarray technology to search for candidate targets in HNSCC.


METHODS
Gene 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.


RESULTS
A total of 192 up-regulated genes at statistical significance of p < 0.01 and log2 ratio > or = 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.


CONCLUSIONS
Five 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.
Han
Jing
J
Tumor Vaccines and Biotechnology Branch, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA. jing.han@fda.hhs.gov
Kioi
Mitomu
M
Chu
Wei-Sing
WS
Kasperbauer
Jan L
JL
Strome
Scott E
SE
Puri
Raj K
RK
D000328:Adult; D000368:Aged; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D051927:CD24 Antigen / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000188:drug therapy / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000032:analysis; D005260:Female; D020869:Gene Expression Profiling; D055551:HSP27 Heat-Shock Proteins / Q000032:analysis; D006258:Head and Neck Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000378:metabolism*; D006360:Heat-Shock Proteins; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones; D020411:Oligonucleotide Array Sequence Analysis
D000944:Antigens, Differentiation, B-Lymphocyte; D051927:CD24 Antigen; C493412:FABP5 protein, human; D050556:Fatty Acid-Binding Proteins; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D000949:Histocompatibility Antigens Class II; D018960:Hyaluronan Receptors; D018832:Molecular Chaperones; C045084:invariant chain