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

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 pro...

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Main Authors: Kaur, Gurjeet, Balasubramaniam, Shandra Devi, Yung, Jen Lee, Balakrishnan, Venugopal, Chern, Ein Oon
Format: Article
Language:English
Published: Asia Pacific Organization for Cancer Prevention (APOCP) 2019
Subjects:
Online Access:http://eprints.usm.my/47610/1/APJCP_Volume%2020_Issue%2010_Pages%203043-3049.pdf
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author Kaur, Gurjeet
Balasubramaniam, Shandra Devi
Yung, Jen Lee
Balakrishnan, Venugopal
Chern, Ein Oon
author_facet Kaur, Gurjeet
Balasubramaniam, Shandra Devi
Yung, Jen Lee
Balakrishnan, Venugopal
Chern, Ein Oon
author_sort Kaur, Gurjeet
collection USM
description 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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spelling usm.eprints-476102020-10-30T20:58:52Z http://eprints.usm.my/47610/ Minichromosome Maintenance Complex (MCM) Genes Profiling and MCM2 Protein Expression in Cervical Cancer Development Kaur, Gurjeet Balasubramaniam, Shandra Devi Yung, Jen Lee Balakrishnan, Venugopal Chern, Ein Oon RC254-282 Neoplasms. Tumors. Oncology (including Cancer) 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. Asia Pacific Organization for Cancer Prevention (APOCP) 2019 Article PeerReviewed application/pdf en http://eprints.usm.my/47610/1/APJCP_Volume%2020_Issue%2010_Pages%203043-3049.pdf Kaur, Gurjeet and Balasubramaniam, Shandra Devi and Yung, Jen Lee and Balakrishnan, Venugopal and Chern, Ein Oon (2019) Minichromosome Maintenance Complex (MCM) Genes Profiling and MCM2 Protein Expression in Cervical Cancer Development. Asian Pacific Journal of Cancer Prevention, 20 (10). pp. 3043-3049. ISSN 2476-762X
spellingShingle RC254-282 Neoplasms. Tumors. Oncology (including Cancer)
Kaur, Gurjeet
Balasubramaniam, Shandra Devi
Yung, Jen Lee
Balakrishnan, Venugopal
Chern, Ein Oon
Minichromosome Maintenance Complex (MCM) Genes Profiling and MCM2 Protein Expression in Cervical Cancer Development
title Minichromosome Maintenance Complex (MCM) Genes Profiling and MCM2 Protein Expression in Cervical Cancer Development
title_full Minichromosome Maintenance Complex (MCM) Genes Profiling and MCM2 Protein Expression in Cervical Cancer Development
title_fullStr Minichromosome Maintenance Complex (MCM) Genes Profiling and MCM2 Protein Expression in Cervical Cancer Development
title_full_unstemmed Minichromosome Maintenance Complex (MCM) Genes Profiling and MCM2 Protein Expression in Cervical Cancer Development
title_short Minichromosome Maintenance Complex (MCM) Genes Profiling and MCM2 Protein Expression in Cervical Cancer Development
title_sort minichromosome maintenance complex mcm genes profiling and mcm2 protein expression in cervical cancer development
topic RC254-282 Neoplasms. Tumors. Oncology (including Cancer)
url http://eprints.usm.my/47610/1/APJCP_Volume%2020_Issue%2010_Pages%203043-3049.pdf
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