Diagnostic value of integrin α3, β4, and β5 gene expression levels for the clinical outcome of tongue squamous cell carcinoma†

BACKGROUND. The objective of the current study was to identify biomarkers that reflect the clinical course of squamous cell carcinoma of the tongue (TSCC). METHODS. TSCC tissue samples from 66 patients were subjected to gene expression analysis by real-time polymerase chain reaction. Eleven integrin family genes and 14 genes used for normalization, including housekeeping genesand genes that encode desmosomal, cytoskeletal, and extracellular matrix molecules, were considered. Multivariate statistical analysis was performed on 154 expression ratios of integrin genes with clinical parameters. RESULTS. In principal-component analysis, the first principal component was related to the outcome of death, and the second principal component mainly reflected the tendency for cervical lymph node(LN) metastasis. The former axis consisted of the variance of the integrin β4 gene (ITGB4) and ITGB5 expression levels, and the latter axis agreed with the expression level of the integrin α3 gene (ITGA3). Multivariate logistic regression analysis with cervical LN metastasis as the response variable concordantly identified ITGA3/junction plakoglobingene (JUP) expression (P = .02) and ITGB5/ paxillingene (PXN) expression (P = .04) as significant factors. Only ITGB4/JUP expression was identified as a significant factor in terms of the outcome of death (P < .00049) by a Cox proportional hazards model. The group with high ITGB4/JUP levels exhibited a significantly high death rate on a Kaplan-Meier curve (P < .0001; Wilcoxon and log-rank tests). CONCLUSIONS. The expression levels of ITGA3, ITGB4, and ITGB5 with functional normalization by desmosomalor cytoskeletal molecule genes were selected as candidate biomarkers for cervical LN metastasis or for the outcome of death in TSCC. Cancer 2008. © 2008 American Cancer Society.