Clinical significance of TC21 overexpression in oral cancer

Muzafar A Macha, Ajay Matta, Uma Sriram, Alok Thakkar, N. K. Shukla, Siddhartha Datta Gupta, Ranju Ralhan

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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, 14-3-3ζ and 14-3-3σ proteins in oral cancer cells. Conclusion: 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, 14-3-3ζ and 14-3-3σ proteins in oral cancer cells and tissues suggests the involvement of TC21 in signaling pathways in oral cancer.

Original languageEnglish (US)
Pages (from-to)477-485
Number of pages9
JournalJournal of Oral Pathology and Medicine
Volume39
Issue number6
DOIs
StatePublished - Jan 1 2010

Fingerprint

Mouth Neoplasms
Leukoplakia
14-3-3 Proteins
Immunoprecipitation
Immunoblotting
ROC Curve
Area Under Curve
Squamous Cell Carcinoma
Proteins
Neoplasms

Keywords

  • R-Ras2
  • TC21
  • dysplasia
  • leukoplakia
  • oral squamous cell carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Pathology and Forensic Medicine
  • Otorhinolaryngology
  • Oral Surgery
  • Periodontics
  • Medicine(all)

Cite this

Macha, M. A., Matta, A., Sriram, U., Thakkar, A., Shukla, N. K., Datta Gupta, S., & Ralhan, R. (2010). Clinical significance of TC21 overexpression in oral cancer. Journal of Oral Pathology and Medicine, 39(6), 477-485. https://doi.org/10.1111/j.1600-0714.2009.00854.x

Clinical significance of TC21 overexpression in oral cancer. / Macha, Muzafar A; Matta, Ajay; Sriram, Uma; Thakkar, Alok; Shukla, N. K.; Datta Gupta, Siddhartha; Ralhan, Ranju.

In: Journal of Oral Pathology and Medicine, Vol. 39, No. 6, 01.01.2010, p. 477-485.

Research output: Contribution to journalArticle

Macha, MA, Matta, A, Sriram, U, Thakkar, A, Shukla, NK, Datta Gupta, S & Ralhan, R 2010, 'Clinical significance of TC21 overexpression in oral cancer', Journal of Oral Pathology and Medicine, vol. 39, no. 6, pp. 477-485. https://doi.org/10.1111/j.1600-0714.2009.00854.x
Macha, Muzafar A ; Matta, Ajay ; Sriram, Uma ; Thakkar, Alok ; Shukla, N. K. ; Datta Gupta, Siddhartha ; Ralhan, Ranju. / Clinical significance of TC21 overexpression in oral cancer. In: Journal of Oral Pathology and Medicine. 2010 ; Vol. 39, No. 6. pp. 477-485.
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abstract = "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, 14-3-3ζ and 14-3-3σ proteins in oral cancer cells. Conclusion: 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, 14-3-3ζ and 14-3-3σ proteins in oral cancer cells and tissues suggests the involvement of TC21 in signaling pathways in oral cancer.",
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