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

January 18, 2017 updated by: Marinka Mravak Stipetic, University of Zagreb

Molecular Mechanisms of Precancerous and Cancerous Lesions of the Oral Cavity

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Actual)

71

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Croatia
      • Zagreb, Croatia, 10000
        • School of Dental Medicine, University of Zagreb

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

A study consisted of 71 consented patients, among which 27 with histologically confirmed diagnosis of oral lichen planus, 23 with oral squamous cell carcinoma and 21 sample of healthy oral mucosa (18 archive samples). Study included 36 male and 35 female patients.

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
oral lichen planus (OLP)

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
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.
Other Names:
  • immunohistochemistry
  • Western blot
oral squamous cell carcinoma (OSCC)

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
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.
Other Names:
  • immunohistochemistry
  • Western blot
healthy mucosa

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
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.
Other Names:
  • immunohistochemistry
  • Western blot

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Zagreb

Collaborators

University of Rijeka

Investigators

  • Principal Investigator: Marinka Mravak-Stipetic, Professor, School of Dental Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2010

Primary Completion (ACTUAL)

December 1, 2014

Study Completion (ACTUAL)

December 1, 2014

Study Registration Dates

First Submitted

January 18, 2017

First Submitted That Met QC Criteria

January 18, 2017

First Posted (ESTIMATE)

January 20, 2017

Study Record Updates

Last Update Posted (ESTIMATE)

January 20, 2017

Last Update Submitted That Met QC Criteria

January 18, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 06509824642532

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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