» Articles » PMID: 37551167

Promoter Methylation Analysis of May Be a Potential Biomarker for Early Detection of Cervical Cancer

Overview
Date 2023 Aug 8
PMID 37551167
Authors
Affiliations
Soon will be listed here.
Abstract

Background: Dickkopf 2 () 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 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 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 was higher in cervical cancer tissue samples. methylation in cervical cancer was significantly higher than that in HSIL (χ = 8.346, = 0.004), whereas methylation in HSIL was significantly higher than that in normal cervical samples (χ = 7.934, = 0.005) and in LSIL samples (χ = 4.375, = 0.037). 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 = 5.239, = 0.022) and low DKK2 mRNA expression (χ = 3.958, = 0.047) compared with patients with no lymph node metastasis. Patients with high-risk human papillomavirus infection exhibited increased promoter methylation frequency (χ = 6.279, = 0.015).

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

Citing Articles

The assessment of Dickkopf-1 and Dickkopf-2 protein concentration in different subtypes of non-small cell lung cancer subtypes.

Hudy D, Gazdzicka J, Swietek A, Golabek K, Rydel M, Czyzewski D Contemp Oncol (Pozn). 2024; 28(1):9-14.

PMID: 38800531 PMC: 11117157. DOI: 10.5114/wo.2024.136981.

References
1.
Uren A, Wolf V, Sun Y, Azari A, Rubin J, Toretsky J . Wnt/Frizzled signaling in Ewing sarcoma. Pediatr Blood Cancer. 2004; 43(3):243-9. DOI: 10.1002/pbc.20124. View

2.
He Y, Su R, Zheng J . Detection of DKK-1 gene methylation in exfoliated cells of cervical squamous cell carcinoma and its relationship with high risk HPV infection. Arch Gynecol Obstet. 2021; 304(3):743-750. DOI: 10.1007/s00404-021-05982-3. View

3.
Schagdarsurengin U, Wilkens L, Steinemann D, Flemming P, Kreipe H, Pfeifer G . Frequent epigenetic inactivation of the RASSF1A gene in hepatocellular carcinoma. Oncogene. 2003; 22(12):1866-71. DOI: 10.1038/sj.onc.1206338. View

4.
Shao Y, Nie X, Song G, Wei Y, Xia P, Xu X . Prognostic value of DKK2 from the Dickkopf family in human breast cancer. Int J Oncol. 2018; 53(6):2555-2565. PMC: 6203157. DOI: 10.3892/ijo.2018.4588. View

5.
Sato H, Suzuki H, Toyota M, Nojima M, Maruyama R, Sasaki S . Frequent epigenetic inactivation of DICKKOPF family genes in human gastrointestinal tumors. Carcinogenesis. 2007; 28(12):2459-66. DOI: 10.1093/carcin/bgm178. View