Molecular Mechanisms of the Development of Precancerous and Cancerous Lesions of the Oral Cavity

Oral Lichen Planus Clinical Trial

Official title:

Molecular Mechanisms of Precancerous and Cancerous Lesions of the Oral Cavity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03026361
• Other study ID #: 06509824642532
• Status: Completed
• Phase: N/A
• First received: January 18, 2017
• Last updated: January 18, 2017
• Start date: January 2010
• Est. completion date: December 2014

Study information

• Verified date: January 2017
• Source: University of Zagreb
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The aim of this study was to examine molecular alterations on the protein level in lesions of oral lichen planus (OLP), oral squamous cell carcinoma (OSCC) and healthy mucosa. Global protein profiling methods based on liquid chromatography coupled to mass spectrometry were used, with a special emphasis on evaluation of deregulated extracellular matrix molecules expression, as well as on analyses of insulin-like growtg factor 2 (IG2F) and insulin-like growth factor 2 receptor (IGFR2) expression in healthy mucosa, OLP and OSCC tissues by comparative semiquantitative immunohistochemistry.

Mass spectrometry based proteomics profiling of healthy mucosa, OLP and OSCC tissues (and accompanied histologically unaltered tissues, respectively) identified 55 extracellular matrix proteins. Twenty among identified proteins were common to all groups of samples. Statistically significant difference between final IGF2 and IGF2R IRS scores in favour to IGF2R may further corroborate the IG2FR antitumor role in OLP and OSCC where it acts as a negative regulator of IGF2 activity.

Description:

Although OLP is categorised as a precancerous condition associated with a significantly increased risk of oral cancer, molecular pathophysiology of OLP and its potential for malignant transformation in OSCC are poorly understood and remain controversial. Development of new analytical methods enhances research in the field of malignant disorders. Identification of novel biomarkers help in the diagnostic process, pre-symptomatic interventions or prediction of treatment response. Proteomics based on mass spectrometry enables analysis of novel, putative biomarkers. In this study, proteomics was used to analyse in more details extracellular matrix (ECM) proteins and proteins related to ECM signalization which have a well-established role in malignant transformation and invasion of tumor cells.

IGF2 and IGF2R are known biomarkers in cellular metabolism,but their role in oral precancerous lesions, namely oral lichen planus (OLP) as well as in oral squamous cell carcinoma (OSCC) has not been explored so far. The second aim of our study was to analyse IG2F and IGFR2 expression in oral lichen planus and oral squamous cell carcinoma tissues by comparative semiquantitative immunohistochemistry

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Years to 70 Years

Eligibility

Inclusion Criteria:

• histopathologically confirmed oral lichen planus and oral squamous cell carcinoma

• healthy volunteers referred for alveolotomy

Exclusion Criteria:

• non-consent patients

• previously treated OSCC

• patients under immunosuppressive therapy

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Lichen Planus
• Lichen Planus, Oral
• Oral Lichen Planus
• Oral Squamous Cell Carcinoma

Intervention

Genetic:
• global proteomic profiling
Global proteomic profiling was performed on OLP and OSCC samples and healthy mucosa. Obtained data was analysed in Uniprot database (http://uniprot.org) with the emphasis on extracellular matrix proteins. In total, 55 extracellular matrix proteins were found to be expressed in analysed samples with very high confidence.

Locations

Country	Name	City	State
Croatia	School of Dental Medicine, University of Zagreb	Zagreb

Sponsors (2)

Lead Sponsor	Collaborator
University of Zagreb	University of Rijeka

Country where clinical trial is conducted

Croatia, 

References & Publications (3)

Pawar H, Kashyap MK, Sahasrabuddhe NA, Renuse S, Harsha HC, Kumar P, Sharma J, Kandasamy K, Marimuthu A, Nair B, Rajagopalan S, Maharudraiah J, Premalatha CS, Kumar KV, Vijayakumar M, Chaerkady R, Prasad TS, Kumar RV, Kumar RV, Pandey A. Quantitative tiss — View Citation

Schiller HB, Szekeres A, Binder BR, Stockinger H, Leksa V. Mannose 6-phosphate/insulin-like growth factor 2 receptor limits cell invasion by controlling alphaVbeta3 integrin expression and proteolytic processing of urokinase-type plasminogen activator rec — View Citation

Zavras AI, Pitiphat W, Wu T, Cartsos V, Lam A, Douglass CW, Diehl SR. Insulin-like growth factor II receptor gene-167 genotype increases the risk of oral squamous cell carcinoma in humans. Cancer Res. 2003 Jan 15;63(2):296-7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Global proteomic profiling of oral lichen planus and oral squamous cell carcinoma		2012-2014
Secondary	evaluation of the Insulin-like growth factor receptor 2 (IGF2R) and IGF2 role in oral lichen planus		2011-2014