Epithelial Mesenchymal Transition Markers in OSMF

NCT ID: NCT03732872

Last Updated: 2018-11-07

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

185 participants

Study Classification

OBSERVATIONAL

Study Start Date

2015-01-15

Study Completion Date

2018-03-20

Brief Summary

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Oral Sub mucous Fibrosis (OSMF) is essentially an imbalance between collagen metabolism and wound healing mechanism induced by arecanut chewing habit. Clinically the disease progresses in stages with patients presenting with burning sensation, intolerance to spicy food, vesicles particularly on the palate, ulceration and dryness of the mouth , fibrosis of the oral mucosa, leading to lips, tongue, and palate rigidity and finally trismus. As the disease is progressively debilitating and has potential to turn in to malignant cancer a study was designed to assess if there any tissue or saliva markers that can be assessed for early diagnosis and indicate malignant transformation if any.

Participants who had OSMF and habit history, patients without OSMF but habit history formed the case group where as normal patients without OSMF and no habit history were in control group. Eligible candidates who consented to participate in study were subjected to biopsy procedure and also their saliva samples were collected. Biopsy samples were subjected to immunohistochemistry (IHC) and polymerase chain reaction (PCR) to assess the EMT markers like vimentin, e-cadherin and collagen IV. miRNA copies were extracted from saliva and were subjected RT-PCR.

Research question was:

1. Is EMT a positive signature in OSMF.
2. Does histopathological grading and dysplasia in OSMF have any correlation with EMT.
3. Can aberrant EMT markers be a reliable indicator for risk assessment of early malignant transformation.
4. Can expression of mi RNA 21 in saliva predict the disease severity and more importantly assess risk of early malignant transformation in OSMF.

Detailed Description

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Epithelial-mesenchymal transition (EMT) describes the process whereby cells shed their epithelial properties and adopt a more mesenchymal and invasive phenotype. A continuous molecular cross talk between epithelial and mesenchymal cells is required during embryonic development (epithelial mesenchymal transition) and probably plays an important role in pathologic process like wound healing and tumour progression. The development of carcinomas is due to the genetic changes within the target epithelium. As there is conversion of normal epithelium to potentially malignant and to squamous cell carcinoma, the stroma also changes from normal to activated or tumor associated called as the stromal reaction. 10 EMT can generate mesenchymal cells that express α-smooth muscle actin (αSMA), as seen in myofibroblasts. It is, however, unclear whether functional myofibroblasts seen in fibrosis or cancer derived from epithelial or endothelial cells

Hence EMT markers in OSMF were assessed in this study. the following markers chosen as:

1. miRNA-21 regulates cell proliferation, apoptosis and the epithelial to mesenchymal transition during neoplastic progression and is up regulated in a variety of cancers.An increased expression of miRNA-21 is seen in myofibroblasts.12 Since we know the role of myofibroblasts in OSMF, salivary expression of mi RNA- 21 was included as marker.
2. Type IV collagen has the unique feature of self-associating through intramolecular covalent bonds, providing barrier and mechanical strength properties to basement membranes.The increased collagen deposition in OSMF involves numerous fibroblasts that are converted to myofibroblasts found in histologic sections of tissue specimens. an altered micro environment or stroma such as persistent myofibroblasts has been shown to result in tumorigenesis and tumor progression
3. Cadherins are a class of type-1 trans-membrane proteins known for its calcium-dependent cell-cell adhesion property. E-cadherins are members of this protein family found in epithelial cells which serve important roles in cell adhesion by ensuring that cells within tissues are bound together. The loss of E-cadherin function or expression has been implicated in cancer progression and metastasis.E-cadherin expression in the head and neck epithelium is essential for the morphogenesis and homeostasis of epithelial tissues. The cadherin-mediated cell-cell contacts are required for the anchorage-dependent growth of epithelial cells.

Hence lower expression of E- cadherin is a sign of loss of epithelial integrity
4. The intermediate filament protein vimentin is involved in the regulation of cell behavior, morphology, and mechanical properties. Vimentin is a EMT marker expressed in connective tissue. Expression of vimentin in epithelium is a positive signature of EMT, and its evaluation in OSMF can unveil the importance of EMT signature in oral fibrosis.

Conditions

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Oral Submucous Fibrosis

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Patient with habits and having OSMF

Patients who had history of arecanut chewing habit in any form and composition and who were not undergone any treatment for their current condition i.e, OSMF

Biopsy tissue analysis

Intervention Type DIAGNOSTIC_TEST

biopsy samples for IHC staining and PCR

Saliva analysis

Intervention Type DIAGNOSTIC_TEST

Saliva samples for miRNA 21 expression analysis

Patients with habits and had no clinical symptoms of OSMF

Patients who had history of arecanut chewing habit in any form and composition and had no symptoms of OSMF clinically

Biopsy tissue analysis

Intervention Type DIAGNOSTIC_TEST

biopsy samples for IHC staining and PCR

Saliva analysis

Intervention Type DIAGNOSTIC_TEST

Saliva samples for miRNA 21 expression analysis

Healthy human volunteers

patients who reported no history of areacnut chewing habits and had no clinical symptoms of OSMF

Biopsy tissue analysis

Intervention Type DIAGNOSTIC_TEST

biopsy samples for IHC staining and PCR

Saliva analysis

Intervention Type DIAGNOSTIC_TEST

Saliva samples for miRNA 21 expression analysis

Interventions

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Biopsy tissue analysis

biopsy samples for IHC staining and PCR

Intervention Type DIAGNOSTIC_TEST

Saliva analysis

Saliva samples for miRNA 21 expression analysis

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Any patient who had history of arecanut chewing habit with clinical manifestations of OSMF.
* Patients who had arecanut chewing habit history of more than 1 year and had no clinical symptoms of OSMF.
* Healthy human volunteers who are indicated for extraction of tooth and had no clinical features of OSMF and had no habit history

Exclusion Criteria

* Patients who had bleeding disorders
* patients who are diagnosed with salivary gland disorders that can alter salivary flow or composition
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Credora Life Sciences, India

UNKNOWN

Sponsor Role collaborator

The Oxford Dental College, Hospital and Research Center, Bangalore, India

OTHER

Sponsor Role lead

Responsible Party

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Dr. Shesha Prasad

Senior lecturer

Responsibility Role PRINCIPAL_INVESTIGATOR

References

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Yang Y, Li YX, Yang X, Jiang L, Zhou ZJ, Zhu YQ. Progress risk assessment of oral premalignant lesions with saliva miRNA analysis. BMC Cancer. 2013 Mar 19;13:129. doi: 10.1186/1471-2407-13-129.

Reference Type BACKGROUND
PMID: 23510112 (View on PubMed)

Sawant SS, Vaidya Mm, Chaukar DA, Alam H, Dmello C, Gangadaran P, Kannan S, Kane S, Dange PP, Dey N, Ranganathan K, D'Cruz AK. Clinical significance of aberrant vimentin expression in oral premalignant lesions and carcinomas. Oral Dis. 2014 Jul;20(5):453-65. doi: 10.1111/odi.12151. Epub 2013 Jul 19.

Reference Type BACKGROUND
PMID: 23865921 (View on PubMed)

Pinto GA, Vassallo J, Andrade LA, Magna LA. Immunohistochemical study of basement membrane collagen IV in uterine cervix carcinoma. Sao Paulo Med J. 1998 Nov-Dec;116(6):1846-51. doi: 10.1590/s1516-31801998000600004.

Reference Type BACKGROUND
PMID: 10349192 (View on PubMed)

Other Identifiers

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Oxford DC

Identifier Type: -

Identifier Source: org_study_id

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