<abstract xmlns="http://www.w3.org/1999/xhtml">

<sec><h3>Background</h3>
<p>Dickkopf 2 (<italic>DKK2</italic>) plays an important role in multiple cancers. Its potential value in the clinical diagnosis of cervical cancer has remained unclear.</p>
</sec>
<sec><h3>Objectives</h3>
<p>To investigate the expression and promoter methylation levels of <italic>DKK2</italic> in cervical cancer and their clinicopathological associations.</p>
</sec>
<sec><h3>Methods</h3>
<p>We used the Gene Expression Omnibus, Oncomine, Cancer Genome Atlas, and University of ALabama at Birmingham CANcer data analysis databases, reverse transcription-PCR, and methylation-specific PCR analysis to predict and examine the expression of DKK2 mRNA and <italic>DKK2</italic> methylation levels in cell lines and cervical cancer tissues from 79 patients with cervical cancer and 63 with cervical precancerous lesions including 25 with low-grade squamous intraepithelial lesions (LSIL) and 38 patients with high-grade squamous intraepithelial lesions (HSIL).</p>
</sec>
<sec><h3>Results</h3>
<p>DKK2 mRNA expression was downregulated in all cancer cell lines and cervical cancer tissues, whereas hypermethylation of <italic>DKK2</italic> was higher in cervical cancer tissue samples. <italic>DKK2</italic> methylation in cervical cancer was significantly higher than that in HSIL (χ<sup>2</sup> = 8.346, <italic>P</italic> = 0.004), whereas <italic>DKK2</italic> methylation in HSIL was significantly higher than that in normal cervical samples (χ<sup>2</sup> = 7.934, <italic>P</italic> = 0.005) and in LSIL samples (χ<sup>2</sup> = 4.375, <italic>P</italic> = 0.037). <italic>DKK2</italic> silencing caused by its promoter hypermethylation was confirmed by treatment with the methyltransferase inhibitor 5-Aza-dC in cell lines. Patients with lymph node metastasis exhibited increased promoter methylation frequency (χ<sup>2</sup> = 5.239, <italic>P</italic> = 0.022) and low DKK2 mRNA expression (χ<sup>2</sup> = 3.958, <italic>P</italic> = 0.047) compared with patients with no lymph node metastasis. Patients with high-risk human papillomavirus infection exhibited increased promoter methylation frequency (χ<sup>2</sup> = 6.279, <italic>P</italic> = 0.015).</p>
</sec>
<sec><h3>Conclusions</h3>
<p><italic>DKK2</italic> epigenetic changes of DKK2 may play a key role in the development of cervical cancer, suggesting that <italic>DKK2</italic> hypermethylation could be used as a triage test for screening, early diagnosis, or risk prediction of cervical cancer.</p>
</sec>
</abstract>

Background
Dickkopf 2 (DKK2) plays an important role in multiple cancers. Its potential value in the clinical diagnosis of cervical cancer has remained unclear.

Objectives
To investigate the expression and promoter methylation levels of DKK2 in cervical cancer and their clinicopathological associations.

Methods
We used the Gene Expression Omnibus, Oncomine, Cancer Genome Atlas, and University of ALabama at Birmingham CANcer data analysis databases, reverse transcription-PCR, and methylation-specific PCR analysis to predict and examine the expression of DKK2 mRNA and DKK2 methylation levels in cell lines and cervical cancer tissues from 79 patients with cervical cancer and 63 with cervical precancerous lesions including 25 with low-grade squamous intraepithelial lesions (LSIL) and 38 patients with high-grade squamous intraepithelial lesions (HSIL).

Results
DKK2 mRNA expression was downregulated in all cancer cell lines and cervical cancer tissues, whereas hypermethylation of DKK2 was higher in cervical cancer tissue samples. DKK2 methylation in cervical cancer was significantly higher than that in HSIL (χ2 = 8.346, P = 0.004), whereas DKK2 methylation in HSIL was significantly higher than that in normal cervical samples (χ2 = 7.934, P = 0.005) and in LSIL samples (χ2 = 4.375, P = 0.037). DKK2 silencing caused by its promoter hypermethylation was confirmed by treatment with the methyltransferase inhibitor 5-Aza-dC in cell lines. Patients with lymph node metastasis exhibited increased promoter methylation frequency (χ2 = 5.239, P = 0.022) and low DKK2 mRNA expression (χ2 = 3.958, P = 0.047) compared with patients with no lymph node metastasis. Patients with high-risk human papillomavirus infection exhibited increased promoter methylation frequency (χ2 = 6.279, P = 0.015).

Conclusions
DKK2 epigenetic changes of DKK2 may play a key role in the development of cervical cancer, suggesting that DKK2 hypermethylation could be used as a triage test for screening, early diagnosis, or risk prediction of cervical cancer.

Promoter methylation analysis of <italic>DKK2</italic> may be a potential biomarker for early detection of cervical cancer

Liaocheng People's Hospital and Liaocheng Clinical School of Shandong First Medical University

Affiliated Hospital of Qingdao University

Institute of Tissue Engineering and Regenerative Medicine

Asian Biomedicine

This work is licensed under the Creative Commons Attribution 4.0 International License.

Promoter methylation analysis of  may be a potential biomarker for early detection of cervical cancer

Background
Dickkopf 2 (DKK2) plays an important role in multiple cancers. Its potential value in the clinical diagnosis of cervical cancer has remained...

Promoter methylation analysis of DKK2 may be a potential biomarker for early detection of cervical cancer

Article Category: Original article

Published Online: Aug 31, 2022

Page range: 181 - 189

DOI: https://doi.org/10.2478/abm-2022-0022

Keywords
biomarkers, data mining, DKK2 protein, human, DNA methylation, human papillomavirus, uterine cervical neoplasms

© 2022 Xian Zhang et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

Promoter methylation analysis of DKK2 may be a potential biomarker for early detection of cervical cancer

Article Category: Original article

Published Online: Aug 31, 2022

Page range: 181 - 189

DOI: https://doi.org/10.2478/abm-2022-0022

Keywordsbiomarkers, data mining, DKK2 protein, human, DNA methylation, human papillomavirus, uterine cervical neoplasms

© 2022 Xian Zhang et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

Keywords
biomarkers, data mining, DKK2 protein, human, DNA methylation, human papillomavirus, uterine cervical neoplasms