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

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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Molecular Mechanisms of Precancerous and Cancerous Lesions of the Oral Cavity

Conditions
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Oral Lichen Planus, Oral Squamous Cell Carcinoma

Intervention / Treatment
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* Genetic: global proteomic profiling


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| oral lichen planus (OLP)<br>Histopathologically confirmed samples of OLP underwent immunohistochemical analysis of IGF2 and IGF2R expression. Fresh-frozen samples of clinically OLP changed and adjacent healthy mucosa underwent global proteomic profiling and two proteins were subsequently validated with Western blot. | Genetic: global proteomic profiling<br>* 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.<br>* Other names: Western blot;|
| oral squamous cell carcinoma (OSCC)<br>Histopathologically confirmed samples of OSCC underwent immunohistochemical analysis of IGF2 and IGF2R expression. Fresh-frozen samples of clinically OSCC changed and adjacent healthy mucosa underwent global proteomic profiling and two proteins were subsequently validated with Western blot. | Genetic: global proteomic profiling<br>* 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.<br>* Other names: Western blot;|
| healthy mucosa<br>Archival samples of healthy oral mucosa underwent immunohistochemical analysis of IGF2 and IGF2R expression. Fresh-frozen samples of healthy mucosa taken during alveolotomy underwent global proteomic profiling and two proteins were subsequently validated with Western blot. | Genetic: global proteomic profiling<br>* 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.<br>* Other names: Western blot;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global proteomic profiling of oral lichen planus and oral squamous cell carcinoma |  | 2012-2014 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| evaluation of the Insulin-like growth factor receptor 2 (IGF2R) and IGF2 role in oral lichen planus |  | 2011-2014 |