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RAP1 GTPase overexpression is associated with cervical intraepithelial neoplasia

Marcelo Antonio Pascoal-Xavier1, Anna Carolina Cançado Figueiredo2, Luciana Inácia Gomes2

  • 1Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil.

Plos One
|April 10, 2015
PubMed

Insights

RAS proximate 1 (RAP1) expression increases with cervical intraepithelial neoplasia (CIN) severity. Higher RAP1 levels significantly elevate the risk for CIN 1 and CIN 2/3, suggesting RAP1 as a potential diagnostic biomarker.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gynecologic Pathology

Background:

  • RAS proximate 1 (RAP1), a GTP-binding protein, is implicated as a potential oncogene due to its high expression in various cancers.
  • The role of RAP1 in the development of cervical cancer (cervical carcinogenesis) has not been previously established.
  • Cervical intraepithelial neoplasia (CIN) represents precancerous changes in the cervix, and understanding molecular drivers is crucial for early detection.

Purpose of the Study:

  • To investigate the association between RAP1 expression and the presence and severity of cervical intraepithelial neoplasia (CIN).
  • To evaluate RAP1 as a potential biomarker for diagnosing CIN.
  • To determine if RAP1 expression levels correlate with the progression of cervical dysplasia.

Main Methods:

  • A cross-sectional study involving 183 paraffin-embedded cervical biopsies.
  • Immunohistochemistry was used for standard and quantitative assessment of RAP1 protein expression.
  • Biopsies were categorized as normal/non-dysplastic mucosa (NDM), CIN grade 1, or CIN grade 2/3.

Main Results:

  • A statistically significant gradual increase in RAP1 expression was observed from NDM to CIN 1 and further to CIN 2/3 (p<0.001).
  • Elevated RAP1 expression was associated with a 3.5-fold increased risk of CIN 1 and a nearly 20-fold increased risk of CIN 2/3 compared to NDM.
  • Ordinal regression analysis indicated that increased RAP1 expression had a stronger association with CIN 2/3 than with CIN 1.

Conclusions:

  • RAP1 expression levels progressively increase with the severity of cervical intraepithelial neoplasia.
  • RAP1 shows potential as a valuable biomarker for the diagnosis of CIN.
  • Further research could explore RAP1's specific role in the molecular pathways of cervical carcinogenesis.

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