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

IF 0.4 4区医学 Q4 MEDICINE, RESEARCH & EXPERIMENTAL

Asian Biomedicine Pub Date : 2022-08-01 DOI:10.2478/abm-2022-0022

Xian Zhang, Aihua Li, Jie Wu, Yu Wu, Xiaoping Ma, Yanjun Liu, Qingfa Chen, Yan Zhang

{"title":"Promoter methylation analysis of DKK2 may be a potential biomarker for early detection of cervical cancer.","authors":"Xian Zhang, Aihua Li, Jie Wu, Yu Wu, Xiaoping Ma, Yanjun Liu, Qingfa Chen, Yan Zhang","doi":"10.2478/abm-2022-0022","DOIUrl":null,"url":null,"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.","PeriodicalId":8501,"journal":{"name":"Asian Biomedicine","volume":null,"pages":null},"PeriodicalIF":0.4000,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10321177/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Asian Biomedicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2478/abm-2022-0022","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 0

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.

Abstract Image

查看原文本刊更多论文

DKK2启动子甲基化分析可能是宫颈癌早期检测的潜在生物标志物。

背景:Dickkopf 2 (DKK2)在多种癌症中发挥重要作用。其在宫颈癌临床诊断中的潜在价值尚不清楚。目的:探讨DKK2在宫颈癌中的表达、启动子甲基化水平及其与临床病理的关系。方法:我们使用了基因表达Omnibus、Oncomine、癌症基因组图谱和阿拉巴马大学伯明翰分校的癌症数据分析数据库、逆转录- pcr、和甲基化特异性PCR分析，预测和检测79例宫颈癌患者和63例宫颈癌前病变患者细胞系和宫颈癌组织中DKK2 mRNA表达和DKK2甲基化水平，其中25例为低级别鳞状上皮内病变(LSIL)， 38例为高级别鳞状上皮内病变(HSIL)。结果:DKK2 mRNA在所有癌细胞系和宫颈癌组织中表达下调，而DKK2高甲基化在宫颈癌组织样本中较高。宫颈癌DKK2甲基化水平显著高于HSIL (χ2 = 8.346, P = 0.004)， HSIL DKK2甲基化水平显著高于正常宫颈样本(χ2 = 7.934, P = 0.005)和LSIL样本(χ2 = 4.375, P = 0.037)。在细胞系中，甲基转移酶抑制剂5-Aza-dC证实了DKK2启动子超甲基化导致的沉默。与未发生淋巴结转移的患者相比，有淋巴结转移的患者启动子甲基化频率增高(χ2 = 5.239, P = 0.022)， DKK2 mRNA表达较低(χ2 = 3.958, P = 0.047)。人乳头瘤病毒感染高危人群启动子甲基化频率增高(χ2 = 6.279, P = 0.015)。结论:DKK2的表观遗传改变可能在宫颈癌的发生发展中发挥关键作用，提示DKK2高甲基化可作为宫颈癌筛查、早期诊断或风险预测的分诊检测指标。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Asian Biomedicine 医学-医学：研究与实验

CiteScore

1.20

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Asian Biomedicine: Research, Reviews and News (ISSN 1905-7415 print; 1875-855X online) is published in one volume (of 6 bimonthly issues) a year since 2007. [...]Asian Biomedicine is an international, general medical and biomedical journal that aims to publish original peer-reviewed contributions dealing with various topics in the biomedical and health sciences from basic experimental to clinical aspects. The work and authorship must be strongly affiliated with a country in Asia, or with specific importance and relevance to the Asian region. The Journal will publish reviews, original experimental studies, observational studies, technical and clinical (case) reports, practice guidelines, historical perspectives of Asian biomedicine, clinicopathological conferences, and commentaries Asian biomedicine is intended for a broad and international audience, primarily those in the health professions including researchers, physician practitioners, basic medical scientists, dentists, educators, administrators, those in the assistive professions, such as nurses, and the many types of allied health professionals in research and health care delivery systems including those in training.