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Characterization of Molecular Markers Indicative of Cervical Cancer Progression.

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 2D-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.

SUBMITTER: Arnouk H

PROVIDER: S-EPMC2761690 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Characterization of Molecular Markers Indicative of Cervical Cancer Progression.

Arnouk Hilal H Merkley Mark A MA Podolsky Robert H RH Stöppler Hubert H Santos Carlos C Alvarez Manuel M Mariategui Julio J Ferris Daron D Lee Jeffrey R JR Dynan William S WS

Proteomics. Clinical applications 20090501 5

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 2D-DIGE. Significant expression changes were seen with 53 spots resulting in identification of 23 uniq ...[more]

PMID: 19834583

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Project description:BackgroundInvasive cervical cancer (ICC) is caused by high-risk human papillomavirus types (HR-HPVs) and is usually preceded by a long phase of intraepithelial neoplasia (CIN). Before invasion, (epi) genetic changes, potentially applicable as molecular markers within cervical screening, occur in HPV host cells. Epigenetic alterations, such as dysregulation of microRNA (miRNA) expression, are frequently observed in ICC. The mechanisms and role of miRNA dysregulation in cervical carcinogenesis are still largely unknown.MethodsWe provide an overview of the studies investigating miRNA expression in relation to ICC progression, highlighting their common outcomes and their weaknesses/strengths. To achieve this, we systematically searched through Pubmed database all articles between January 2010 and December 2017.ResultsFrom the 24 studies retrieved, miR-29a and miR-21 are the most frequently down- and up-regulated in ICC progression, respectively. Microarray-based studies show a small overlap, with miR-10a, miR-20b, miR-9, miR-16 and miR-106 found repeatedly dysregulated. miR-34a, miR-125 and miR-375 were also found dysregulated in cervical exfoliated cells in relation to cancer progression.ConclusionsThe pivotal role of miRNAs in ICC progression and initial development is becoming more and more relevant. Available studies are essentially based on convenience material, entailing possible selection bias, and frequently of small size: all these points still represent a limitation to a wide comprehension of miRNAs relevant for ICC. The targeted approach instead of a genome-wide investigation still precludes the identification of all the relevant miRNAs in the process. The implementation of deep sequencing on large scale population-based studies will help to discover and validate the relation between altered miRNA expression and CC progression for the identification of biomarkers. Optimally, once explored on a miRNome scale, small specific miRNA signatures maybe used in the context of screening.

Dataset Information

Characterization of Molecular Markers Indicative of Cervical Cancer Progression.

Publications

Characterization of Molecular Markers Indicative of Cervical Cancer Progression.

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