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

Completed

• Conditions: Oral Lichen Planus; Oral Squamous Cell Carcinoma
• Interventions: Genetic: global proteomic profiling

• Registration Number: NCT03026361
• Lead Sponsor: University of Zagreb

Brief 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.

Detailed 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

Study Timeline

• Study Start: 2010-01
• Primary Completion: 2014-12
• Study Completion: 2014-12
• Status Verified: 2017-01
• Study First Submitted: 2017-01-18
• Study First Submitted QC: 2017-01-18
• Last Update Submitted: 2017-01-18
• Study First Posted: 2017-01-20
• Last Update Posted: 2017-01-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 71

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
oral lichen planus (OLP)	global proteomic profiling	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.
oral squamous cell carcinoma (OSCC)	global proteomic profiling	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.
healthy mucosa	global proteomic profiling	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.

Primary Outcome Measures

Name	Time	Method
Global proteomic profiling of oral lichen planus and oral squamous cell carcinoma	2012-2014

Secondary Outcome Measures

Name	Time	Method
evaluation of the Insulin-like growth factor receptor 2 (IGF2R) and IGF2 role in oral lichen planus	2011-2014

Trial Locations

Locations (1)

School of Dental Medicine, University of Zagreb; 🇭🇷 Zagreb, Croatia