mRNA-lncRNA gene expression signature in HPV-associated neoplasia and cervical cancer

Cervical cancer is one of the most frequent cancers in women and is associated with human papillomavirus (HPV) in 70 % of cases. Cervical cancer occurs because of progression of low-differentiated cervical intraepithelial neoplasia through grade 2 and 3 lesions. Along with the protein-coding genes,...

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Main Authors: E. D. Kulaeva, E. S. Muzlaeva, E. V. Mashkina
Format: Article
Language:English
Published: Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders 2024-05-01
Series:Вавиловский журнал генетики и селекции
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Online Access:https://vavilov.elpub.ru/jour/article/view/4148
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author E. D. Kulaeva
E. S. Muzlaeva
E. V. Mashkina
author_facet E. D. Kulaeva
E. S. Muzlaeva
E. V. Mashkina
author_sort E. D. Kulaeva
collection DOAJ
description Cervical cancer is one of the most frequent cancers in women and is associated with human papillomavirus (HPV) in 70 % of cases. Cervical cancer occurs because of progression of low-differentiated cervical intraepithelial neoplasia through grade 2 and 3 lesions. Along with the protein-coding genes, long noncoding RNAs (lncRNAs) play an important role in the development of malignant cell transformation. Although human papillomavirus is widespread, there is currently no well-characterized transcriptomic signature to predict whether this tumor will develop in the presence of HPV-associated neoplastic changes in the cervical epithelium. Changes in gene activity in tumors reflect the biological diversity of cellular phenotype and physiological functions and can be an important diagnostic marker. We performed comparative transcriptome analysis using open RNA sequencing data to assess differentially expressed genes between normal tissue, neoplastic epithelium, and cervical cancer. Raw data were preprocessed using the Galaxy platform. Batch effect correction, identification of differentially expressed genes, and gene set enrichment analysis (GSEA) were performed using R programming language packages. Subcellular localization of lncRNA was analyzed  using Locate-R and iLoc-LncRNA 2.0 web services. 1,572 differentially expressed genes (DEGs) were recorded in the “cancer vs. control” comparison, and 1,260 DEGs were recorded in the “cancer vs. neoplasia” comparison. Only two genes were observed to be differentially expressed in the “neoplasia vs. control” comparison. The search for common genes among the most strongly differentially expressed genes among all comparison groups resulted in the identification of an expression signature consisting of the CCL20, CDKN2A, CTCFL, piR-55219, TRH, SLC27A6 and EPHA5 genes. The transcription level of the CCL20 and CDKN2A genes becomes increased at the stage of neoplastic epithelial changes and stays so in cervical cancer. Validation on an independent microarray dataset showed that the differential expression patterns of the CDKN2A and SLC27A6 genes were conserved in the respective gene expression comparisons between groups.
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institution Kabale University
issn 2500-3259
language English
publishDate 2024-05-01
publisher Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
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series Вавиловский журнал генетики и селекции
spelling doaj-art-c763718a198241898b2299c7853be72b2025-02-01T09:58:13ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592024-05-0128334235010.18699/vjgb-24-391469mRNA-lncRNA gene expression signature in HPV-associated neoplasia and cervical cancerE. D. Kulaeva0E. S. Muzlaeva1E. V. Mashkina2Southern Federal UniversitySouthern Federal UniversitySouthern Federal UniversityCervical cancer is one of the most frequent cancers in women and is associated with human papillomavirus (HPV) in 70 % of cases. Cervical cancer occurs because of progression of low-differentiated cervical intraepithelial neoplasia through grade 2 and 3 lesions. Along with the protein-coding genes, long noncoding RNAs (lncRNAs) play an important role in the development of malignant cell transformation. Although human papillomavirus is widespread, there is currently no well-characterized transcriptomic signature to predict whether this tumor will develop in the presence of HPV-associated neoplastic changes in the cervical epithelium. Changes in gene activity in tumors reflect the biological diversity of cellular phenotype and physiological functions and can be an important diagnostic marker. We performed comparative transcriptome analysis using open RNA sequencing data to assess differentially expressed genes between normal tissue, neoplastic epithelium, and cervical cancer. Raw data were preprocessed using the Galaxy platform. Batch effect correction, identification of differentially expressed genes, and gene set enrichment analysis (GSEA) were performed using R programming language packages. Subcellular localization of lncRNA was analyzed  using Locate-R and iLoc-LncRNA 2.0 web services. 1,572 differentially expressed genes (DEGs) were recorded in the “cancer vs. control” comparison, and 1,260 DEGs were recorded in the “cancer vs. neoplasia” comparison. Only two genes were observed to be differentially expressed in the “neoplasia vs. control” comparison. The search for common genes among the most strongly differentially expressed genes among all comparison groups resulted in the identification of an expression signature consisting of the CCL20, CDKN2A, CTCFL, piR-55219, TRH, SLC27A6 and EPHA5 genes. The transcription level of the CCL20 and CDKN2A genes becomes increased at the stage of neoplastic epithelial changes and stays so in cervical cancer. Validation on an independent microarray dataset showed that the differential expression patterns of the CDKN2A and SLC27A6 genes were conserved in the respective gene expression comparisons between groups.https://vavilov.elpub.ru/jour/article/view/4148human papillomavirusneoplasiacervical cancertranscriptome analysislncrnacdkn2accl20
spellingShingle E. D. Kulaeva
E. S. Muzlaeva
E. V. Mashkina
mRNA-lncRNA gene expression signature in HPV-associated neoplasia and cervical cancer
Вавиловский журнал генетики и селекции
human papillomavirus
neoplasia
cervical cancer
transcriptome analysis
lncrna
cdkn2a
ccl20
title mRNA-lncRNA gene expression signature in HPV-associated neoplasia and cervical cancer
title_full mRNA-lncRNA gene expression signature in HPV-associated neoplasia and cervical cancer
title_fullStr mRNA-lncRNA gene expression signature in HPV-associated neoplasia and cervical cancer
title_full_unstemmed mRNA-lncRNA gene expression signature in HPV-associated neoplasia and cervical cancer
title_short mRNA-lncRNA gene expression signature in HPV-associated neoplasia and cervical cancer
title_sort mrna lncrna gene expression signature in hpv associated neoplasia and cervical cancer
topic human papillomavirus
neoplasia
cervical cancer
transcriptome analysis
lncrna
cdkn2a
ccl20
url https://vavilov.elpub.ru/jour/article/view/4148
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AT esmuzlaeva mrnalncrnageneexpressionsignatureinhpvassociatedneoplasiaandcervicalcancer
AT evmashkina mrnalncrnageneexpressionsignatureinhpvassociatedneoplasiaandcervicalcancer