Diagnostic value of integrin alpha3, beta4, and beta5 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 genes and 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 beta4 gene (ITGB4) and ITGB5 expression levels, and the latter axis agreed with the expression level of the integrin alpha3 gene (ITGA3). Multivariate logistic regression analysis with cervical LN metastasis as the response variable concordantly identified ITGA3/junction plakoglobin gene (JUP) expression (P=.02) and ITGB5/paxillin gene (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 desmosomal or cytoskeletal molecule genes were selected as candidate biomarkers for cervical LN metastasis or for the outcome of death in TSCC.
Kurokawa
Akira
A
Division of Oral and Maxillofacial Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Nagata
Masaki
M
Kitamura
Nobutaka
N
Noman
Arhab A
AA
Ohnishi
Makoto
M
Ohyama
Tokio
T
Kobayashi
Takanori
T
Shingaki
Susumu
S
Takagi
Ritsuo
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D051180:Desmoplakins / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D039422:Integrin alpha3 / Q000235:genetics* / Q000378:metabolism; D039641:Integrin beta Chains / Q000235:genetics* / Q000378:metabolism; D039663:Integrin beta4 / Q000235:genetics* / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D051419:Paxillin / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014062:Tongue Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051185:gamma Catenin
D051180:Desmoplakins; C059834:ITGB4 protein, human; D039422:Integrin alpha3; D039641:Integrin beta Chains; D039663:Integrin beta4; C495292:JUP protein, human; C496061:PXN protein, human; D051419:Paxillin; D012333:RNA, Messenger; D051185:gamma Catenin; C084344:integrin beta5