Searching for the methylation sites involved in human papillomavirus type 16 and 18‑positive women with cervical cancer

Yanyun Ma; Chunxia Wang; Mengqi Shi; Mingshan Li; Lin Li; Tuanjie Che; Jing Qu

doi:10.3892/mco.2022.2582

Searching for the methylation sites involved in human papillomavirus type 16 and 18‑positive women with cervical cancer

Mol Clin Oncol. 2022 Sep 2;17(4):149. doi: 10.3892/mco.2022.2582. eCollection 2022 Oct.

Authors

Yanyun Ma¹, Chunxia Wang¹, Mengqi Shi², Mingshan Li², Lin Li³, Tuanjie Che³, Jing Qu²

Affiliations

¹ Clinical Laboratory, The First People's Hospital of Lanzhou, Lanzhou, Gansu 730050, P.R. China.
² Department of Cell Biology, School of Biology and Basic of Medical Science, Medical College of Soochow University, Suzhou, Jiangsu 215153, P.R. China.
³ Laboratory of Precision Medicine and Translational Medicine, Suzhou Science and Technology Town Hospital, Suzhou, Jiangsu 215153, P.R. China.

Abstract

It has been reported that >90% of women with cervical cancer are human papillomavirus (HPV)-positive, with HPV16 and 18 being the most 'highest-risk' HPV genotypes. However, in numerous women, HPV infection will not progress to cervical cancer. Accordingly, more appropriate screening markers need to be explored. In the present study, genome-wide DNA methylomic differences between cervical cancer tissues with HPV-16 or HPV-18 infection and normal cervical tissues were detected by using an Illumina Human Methylation 850 K BeadChip. The Gene Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted in order to define the nearest neighbouring genes of differentiated methylation sites. Moreover, differentiated methylation sites were verified using pyrosequencing. KEGG analyses suggested that the focal adhesion pathway and pathways in cancer were highly enriched. Bioinformatics and statistical analysis indicated that the nine CpG loci had the most significant differences amongst the genes involved in these pathways. Among these, six CpG sites in the CHRM2, LAMA4, COL11A1, FGF10, IGF1 and TEK genes were highly associated with HPV-16-positive cervical cancer, as validated using pyrophosphate sequencing. Additionally, 10 significantly different CpG sites of the HPV-18-positive group were selected and verified in The Cancer Genome Atlas, indicating their possible diagnostic roles in cervical cancer development and determination. In addition, eight hypermethylated CpG island sites that were associated with HPV-16-positive cervical cancer tissues and 10 hypermethylated CpG island sites that were associated with HPV-18-positive cervical cancer tissues were identified, highlighting their potential roles in screening and evaluating targeted therapy efficacy and prognosis. The main focus of the present study was to identify the genetic variability in HPV-16- and HPV-18-positive samples and to elucidate possible methylation biomarkers in HPV-positive women with a risk of developing cervical cancer.

Keywords: biomarker; cervical cancer; human papillomavirus 16; human papillomavirus 18; methylation.

Grants and funding

Funding: The present study was supported by the innovation and entrepreneurship talent project of Lanzhou (2015-RC-68), distinguished professorship program of national research program on prevention and control of major birth defects in reproductive health (2017YFC1000900), special-funded program on national key scientific instruments and equipment development (2016YFF0103800), health and family planning commission research project of Jiangsu province (H201619).