Characterization of molecular markers indicative of cervical cancer progression

Hilal Arnouk, Mark A. Merkley, Robert H. Podolsky, Hubert Stöppler, Carlos Santos, Manuel Álvarez, Julio Mariategui, Daron Ferris, Jeffrey R. Lee, William S. Dynan

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Cervical cancer originates with human papillomavirus (HPV) infection and progresses via histologically defined premalignant stages. Here we compare normal cervical epithelium and patient-matched high-grade squamous intraepithelial lesions (HSIL) with cervical carcinoma tissue from the same patient population (n = 10 per group). Specimens were analyzed by combined laser capture microdissection and 2-D DIGE. Significant expression changes were seen with 53 spots resulting in identification of 23 unique proteins at the molecular level. These include eight that uniquely distinguish normal epithelium and HSIL and four that uniquely distinguish HSIL and carcinoma. In addition, one protein, cornulin, distinguishes all three states. Other identified proteins included differentiation markers, oncogene DJ-1, serpins, stress and interferon-responsive proteins, detoxifying enzymes, and serum transporters. A literature review, performed for all identified proteins, allowed most changes to be assigned to one of three causes: direct or indirect HPV oncoprotein interactions, growth selection during latency, or interactions in the lesion microenvironment. Selected findings were confirmed by immunohistochemistry using either frozen sections from the same cohort or formalin fixed paraffin embedded samples from a tissue microarray. Novel markers described here have potential applications for increasing the predictive value of current screening methods.

Original languageEnglish (US)
Pages (from-to)516-527
Number of pages12
JournalProteomics - Clinical Applications
Volume3
Issue number5
DOIs
StatePublished - 2009

Keywords

  • 2-D DIGE
  • Cervical cancer
  • High-grade squamous intraepithelial lesion (HSIL)
  • Human papillomavirus
  • Laser capture microdissection

ASJC Scopus subject areas

  • Clinical Biochemistry

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  • Cite this

    Arnouk, H., Merkley, M. A., Podolsky, R. H., Stöppler, H., Santos, C., Álvarez, M., Mariategui, J., Ferris, D., Lee, J. R., & Dynan, W. S. (2009). Characterization of molecular markers indicative of cervical cancer progression. Proteomics - Clinical Applications, 3(5), 516-527. https://doi.org/10.1002/prca.200800068