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Use of Pap Smear Derived Cells to Analyze the Expression of SLC6A14 and GPR81 Genes

Sponsor
Texas Tech University Health Sciences Center (Other)
Overall Status
Terminated
CT.gov ID
NCT03039868
Collaborator
(none)
180
Enrollment
18
Actual Duration (Months)

Study Details

Study Description

Brief Summary

SLC6A14 may serve as a biomarker for cervical dysplasia or cervical cancer.

Condition or Disease Intervention/Treatment Phase

    Detailed Description

    SLC6A14 amino acid transporter Previous research has shown that the expression of the amino acid transporter SLC6A14 is up-regulated in cervical cancer1. Studies on breast, colon and pancreatic cancer cells have shown that SLC6A14 amino acid transporter serves the role of supporting amino acid nutrition to these cancer cells2,3,4. It has also been shown that genetic deletion or pharmacologic blockade of the above transporter will suppress the growth of the tumor cells both in vitro and in vivo4,5,6.

    We are interested in exploring the expression of SLC6A14 transporter in normal cervical epithelial cells, in cervical dysplasia and cervical cancer; and to see if expression of this transporter has any correlation to presence/severity of cervical dysplasia/cancer, and also to see if this may serve as a biomarker to predict or diagnose the presence of cervical dysplasia and cervical cancer.

    GPR81, a G-protein coupled receptor for lactate Human vagina is predominantly colonized by Lactobacilli, which convert glycogen in the vaginal epithelial cells to lactic acid. Some species of Lactobacilli also produce hydrogen peroxide. Both lactate and H2O2 help to keep the vaginal pH low (acidic <4.5) and also help in preventing colonization of the vagina by pathogenic bacteria. When the levels of Lactobacilli in the vaginal micro environment change (as with certain vaginal infections, decline in estrogen levels etc), levels of lactate decline and H2O2 decline-thus predisposing women to vaginal infections.

    Vaginal and cervical fluids contain lactate in millimolar concentrations. Recent studies have identified a G-protein-coupled cell-surface receptor for lactate,-called GPR81. Studies from Dr. Ganapathy's lab have shown that activation of the receptor GPR81 in B lymphocytes enhances the production of IgA antibody, which plays a role in defense mechanisms of mucosal surfaces. IgA antibodies are seen in high levels in the intestinal, colonic, lung mucosa as well as vaginal epithelial surfaces. These IgA antibodies protect the colonization of mucosal surfaces by pathogenic bacteria. Thus GPR 81 is an anti-inflammatory molecule. Hence it may inversely correlate with cervical dysplasia. We propose to investigate if the vaginal and cervical epithelial cells express this GPR81, whether GPR81 expression correlates to cervical dysplasia.

    If a correlation exists between lactate levels and GPR81 expression, declining Lactobacilli levels with associated decline in lactate levels, could lead to decreased GPR81 expression on epithelial cells, and thus decline in IgA antibody secretion. This could be the reason for vaginal infections with decreased Lactobacilli. If infection with HPV virus occurs, this will lead to abnormalities in the Pap smear and potential cervical dysplasia in the future.

    Study Design

    Study Type:
    Observational
    Actual Enrollment :
    180 participants
    Observational Model:
    Case-Control
    Time Perspective:
    Prospective
    Official Title:
    Use of Pap Smear Derived Cells to Analyze the Expression of SLC6A14 and GPR81 Genes
    Actual Study Start Date :
    Dec 1, 2016
    Actual Primary Completion Date :
    May 1, 2018
    Actual Study Completion Date :
    Jun 1, 2018

    Arms and Interventions

    Arm Intervention/Treatment
    Normal Pap smears

    This is the control group.
    Abnormal Pap smears

    This is the case group.

    Outcome Measures

    Primary Outcome Measures

    1. Expression of SLC6A14 and GPR81 transporter in cervical epithelial cells measured as "delta Ct" to correlate expression levels to cervical dysplasia and cervical cancer [Prospective study over a period of 3 years.]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    21 Years to 90 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    1. Women who present to the TTUHSC Lubbock OBGYN Clinics for exams and are having cervical Pap smear collected as part of the evaluations.

    2. Women who have vaginal discharge will be also included in the study if they are having cervical Pap smear collected as part of their exam.

    3. Age criteria 21yr- 65yrs or more -per ASCCP guidelines for Pap smears.

    4. Patients on any medications will also be included- medications have no effect on Pap smear results.

    Exclusion Criteria:

    1. Women who have had a hysterectomy.

    2. Women having vaginal Pap smears.

    3. Women with known HIV.

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Texas Tech University Health Sciences Center

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Texas Tech University Health Sciences Center
    ClinicalTrials.gov Identifier:
    NCT03039868
    Other Study ID Numbers:
    • L17-030
    First Posted:
    Feb 1, 2017
    Last Update Posted:
    Nov 13, 2019
    Last Verified:
    Nov 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No

    Study Results

    No Results Posted as of Nov 13, 2019