Clinical significance of TC21 overexpression in oral cancer.
BACKGROUND
In search of novel molecular markers for oral cancer, we reported increased levels of TC21/R-Ras2 transcripts in oral squamous cell carcinoma by differential display. The aim of this study was to determine the clinical significance of TC21 in oral cancer.


METHODS
Immunohistochemical analysis of TC21 protein expression was carried out in 120 leukoplakias, 83 OSCCs and 30 non-malignant tissues, confirmed by immunoblotting, and correlated with clinicopathological parameters as well as disease prognosis. Co-immunoprecipitation assays were carried out to identify the interaction partners of TC21 protein in oral cancer cells and tissues.


RESULTS
TC21 nuclear expression increased from normal oral tissues to leukoplakia and frank malignancy (P < 0.001). TC21 overexpression was observed in 74.2% leukoplakia with no dysplasia, 75.9% dysplasias and 79.5% OSCCs in comparison with normal oral tissues. Receiver operating characteristic analysis showed that the area-under-the curve values were 0.895, 0.885, and 0.919, while the positive predictive values were 95.8%, 95.6%, and 97.1%, for nuclear immunostaining for normal versus leukoplakia with no dysplasia, leukoplakic lesions with dysplasia, and OSCCs, respectively. Immunoblotting confirmed overexpression of TC21 in oral lesions. Using co-immunoprecipitation assays, we showed interactions of TC21 with Erk2, PI3-K, 14-3-3zeta and 14-3-3sigma proteins in oral cancer cells.


CONCLUSIONS
Our findings suggested that alteration in TC21 expression is an early event in oral cancer and correlates with poor prognosis of OSCCs. TC21 interactions with Erk2, PI3-K, 14-3-3zeta and 14-3-3sigma proteins in oral cancer cells and tissues suggests the involvement of TC21 in signaling pathways in oral cancer.
Macha
Muzafar A
MA
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
Matta
Ajay
A
Sriram
Uma
U
Thakkar
Alok
A
Shukla
N K
NK
Datta Gupta
Siddhartha
S
Ralhan
Ranju
R
D048948:14-3-3 Proteins / Q000378:metabolism; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D018572:Disease-Free Survival; D005092:Exonucleases / Q000378:metabolism; D005095:Exoribonucleases; D015870:Gene Expression; D006801:Humans; D047468:Immunoprecipitation; D053208:Kaplan-Meier Estimate; D007972:Leukoplakia, Oral / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D020559:Monomeric GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011379:Prognosis; D012372:ROC Curve; D015398:Signal Transduction; D015854:Up-Regulation
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D019869:Phosphatidylinositol 3-Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human; C087360:RRAS2 protein, human; D020559:Monomeric GTP-Binding Proteins