Minichromosome Maintenance Complex (MCM) Genes Profiling and MCM2 Protein Expression in Cervical Cancer Development

Document Type: Research Articles

Authors

Institute for Research in Molecular Medicine, Universiti Sains Malaysia, 11800 Minden, Pulau Pinang, Malaysia.

Abstract

Objective: Minichromosome maintenance complex (MCM) proteins are essential for the process of DNA replication
and cell division. This study aimed to evaluate MCM genes expression profiles and MCM2 protein in HPV-associated
cervical carcinogenesis. Methodology: MCM2, 4, 5 and 7 genes expression profiles were evaluated in three cervical
tissue samples each of normal cervix, human papillomavirus (HPV)-infected low grade squamous intraepithelial
lesion (LSIL), high grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC), using Human
Transcriptome Array 2.0 and validated by nCounter® PanCancer Pathway NanoString Array. Immunohistochemical
expression of MCM2 protein was semi-quantitatively assessed by histoscore in tissue microarrays containing 9 cases of
normal cervix, 10 LSIL, 10 HSIL and 42 cases of SCC. Results: MCM2, 4, 5 and 7 genes expressions were upregulated
with increasing fold change during the progression from LSIL to HSIL and the highest in SCC. MCM2 gene had the
highest fold change in SCC compared to normal cervix. Immunohistochemically, MCM2 protein was localised in
the nuclei of basal cells of normal cervical epithelium and dysplastic-neoplastic cells of CIN and SCC. There was a
significant difference in MCM2 protein expression between the histological groups (P = 0.039), and histoscore was the
highest in HSIL compared to normal cervix (P = 0.010). Conclusion: The upregulation of MCM genes expressions in
cervical carcinogenesis reaffirms MCM as a proliferative marker in DNA replication pathway, whereby proliferation of
dysplastic and cancer cells become increasingly dysregulated and uncontrolled. A strong expression of MCM2 protein
in HSIL may aid as a concatenated screening tool in detecting pre-cancerous cervical lesions.

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