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

NCT ID: NCT03026361

Last Updated: 2017-01-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

71 participants

Study Classification

OBSERVATIONAL

Study Start Date

2010-01-31

Study Completion Date

2014-12-31

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

Conditions

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Oral Lichen Planus Oral Squamous Cell Carcinoma

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

global proteomic profiling

Intervention Type GENETIC

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.

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.

global proteomic profiling

Intervention Type GENETIC

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.

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.

global proteomic profiling

Intervention Type GENETIC

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.

Interventions

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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.

Intervention Type GENETIC

Other Intervention Names

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immunohistochemistry Western blot

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
Minimum Eligible Age

30 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Rijeka

OTHER

Sponsor Role collaborator

University of Zagreb

OTHER

Sponsor Role lead

Responsible Party

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Marinka Mravak Stipetic

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Marinka Mravak-Stipetic, Professor

Role: PRINCIPAL_INVESTIGATOR

University of Zagreb

Locations

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School of Dental Medicine, University of Zagreb

Zagreb, , Croatia

Site Status

Countries

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Croatia

References

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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 receptor. Mol Biol Cell. 2009 Feb;20(3):745-56. doi: 10.1091/mbc.e08-06-0569. Epub 2008 Nov 26.

Reference Type RESULT
PMID: 19037107 (View on PubMed)

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.

Reference Type RESULT
PMID: 12543777 (View on PubMed)

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 tissue proteomics of esophageal squamous cell carcinoma for novel biomarker discovery. Cancer Biol Ther. 2011 Sep 15;12(6):510-22. doi: 10.4161/cbt.12.6.16833. Epub 2011 Sep 15.

Reference Type RESULT
PMID: 21743296 (View on PubMed)

Other Identifiers

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06509824642532

Identifier Type: -

Identifier Source: org_study_id

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