High methylation of ZNF582 in cervical adenocarcinoma affects radiosensitivity and prognosis

Wu, Na-Yi Yuan; Zhang, Xiaoyun; Chu, Tang-Yuan; Zhu, Shengtao; Deng, Yuping; Zhou, Yi; Wang, Ying; Zhao, Xueheng; Liu, Lu; Fang, Chao; Wang, Yang; Liou, Yu-Ligh; Cai, Jifeng; Wang, Jing

doi:10.21037/atm.2019.06.15

Cited by 18 publications

(14 citation statements)

References 30 publications

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“…Furthermore, the two genes are totally different in DNA sequences when using NCBI BLAST to compare. Several studies reported that ZNF582 expression was low in cancer, and low expression was associated with promoter hypermethylation and disease outcomes [ 29 , 30 , 31 , 32 , 33 , 34 ]. To assess if the two genes have any relationship in expression, we analyzed their correlation in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

LncRNA ZNF582-AS1 Expression and Methylation in Breast Cancer and Its Biological and Clinical Implications

Wang

Katsaros²,

Biglia³

et al. 2022

Cancers

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Background: Long non-coding RNAs (lncRNAs) play an important role in cellular activities and functions, but our understanding of their involvement in cancer is limited. Methods: TCGA data on RNA expression and DNA methylation were analyzed for lncRNAs’ association with breast cancer survival, using the Cox proportional hazard regression model. Fresh tumor samples and clinical information from 361 breast cancer patients in our study were used to confirm the TCGA finding on ZNF582-AS1. A RT-qPCR method was developed to measure ZNF582-AS1 expression. Survival associations with ZNF582-AS1 were verified with a meta-analysis. In silico predictions of molecular targets and cellular functions of ZNF582-AS1 were performed based on its molecular signatures and nucleotide sequences. Results: ZNF582-AS1 expression was lower in breast tumors than adjacent normal tissues. Low ZNF582-AS1 was associated with high-grade or ER-negative tumors. Patients with high ZNF582-AS1 had a lower risk of relapse and death. These survival associations were confirmed in a meta-analysis and remained significant after adjustment for tumor grade, disease stage, patient age, and hormone receptor status. Correlation analysis indicated the possible suppression of ZNF582-AS1 expression by promoter methylation. Bioinformatics interrogation of molecular signatures suggested that ZNF582-AS1 could suppress tumor cell proliferation via downregulating the HER2-mediated signaling pathway. Analysis of online data also suggested that HIF-1-related transcription factors could suppress ZNF582-AS1 expression, and the lncRNA might bind to hsa-miR-940, a known oncogenic miRNA in breast cancer. Conclusions: ZNF582-AS1 may play a role in suppressing breast cancer progression. Elucidating the lncRNA’s function and regulation may improve our understanding of the disease.

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Section: Discussionmentioning

confidence: 99%

LncRNA ZNF582-AS1 Expression and Methylation in Breast Cancer and Its Biological and Clinical Implications

Wang

Katsaros²,

Biglia³

et al. 2022

Cancers

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“…Antwih et al 25 found that ionizing radiations significantly altered the level of gene methylation by downregulating DNMT2 in breast cancer cells. Wu et al 24 reported that ZNF582 methylation levels decreased in patients receiving neoadjuvant radiotherapy. However, few studies have reported the functional of PAX1 methylation during CCRT.…”

Section: Discussionmentioning

confidence: 99%

“…David Guerrero-Setas et al [23] reported that a significant correlation between RASSF2 hypermethylation and bad prognosis of cervical cancer. Wu et al [24] demonstrated that ZNF582 negative could increase resistance to radiation and affect the prognosis. Meanwhile, Ph Su et al [21] analyzed DNA methylation from TCGA database that disease-free survival (PFS) and overall survival (OS) of patients with the hypermethylated PAX1 gene was significantly shorter than the hypomethylated patients in uterine cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

Methylation of PAX1 gene promoter in the prediction of concurrent chemo-radiotherapy efficacy in cervical cancer

Li¹,

Zhou²,

Zeng³

et al. 2021

J. Cancer

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Objectives: Cervical cancer is the fourth leading cause of cancer death among women worldwide. In currently, aberrant methylation of PAX1 is found in variety of solid tumors, including cervical cancer. In addition, the role of PAX1 gene methylation in cervical cancer and precancerous lesions screening has been confirmed in previous study. Here, we evaluated the predictive value of PAX1 methylation in concurrent chemo-radiotherapy (CCRT) outcomes in cervical cancer. Methods: This study enrolled 82 cervical cancer patients from August 2018 to August 2020. We compared the clinical results between different PAX1 methylation status. Hyper-methylation patients were subjects to MRI and quantitative methylation-specific PCR (QMSP) for PAX1 before, in the middle, immediately after, 1 month and 3 months after CCRT. The changes in PAX1 methylation during CCRT were analyzed. Results: The lower PAX1 methylation status were related to a poor tumor response. Based on the MRI findings three months post-treatment, the hypermethylated patients were classified into the complete response (CR; n=50) and partial remission (PR; n=18) groups. The average PAX1 △Cp value of CR and PR groups before radiotherapy was 5.08±1.98 and 4.32±2.00 respectively, and after concurrent chemo-radiotherapy was significantly increased to 17.35±4.96 and 16.99±6.17, respectively (P<0.05). Furthermore, the PAX1 △Cp value between CR and PR groups were significantly different at mid-treatment and performed well in predicting short-term efficacy (AUC 0.84) in this period, and its sensitivity and specificity for predicting PR were 0.72 and 0.88, respectively. Conclusion: The PAX1 methylation level may predict the sensitivity and efficacy of CCRT in cervical cancer.

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“…[40] Aberrantly high methylation of ZNF582 may even be a potential biomarker for determining ADC prognosis and chemoradiotherapy resistance. [41] Hence, a larger sample with multiple subtypes of ADC is needed to verify and con rm the differences between methylation assessment and hrHPV testing for ADC diagnosis.…”

Section: Discussionmentioning

confidence: 99%

DNA methylation for cervical cancer screening: A validation trial in China

Kong¹,

Wang²,

Wang³

et al. 2020

Preprint

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Background Based on published results from a training set, EPB41L3 and JAM3 gene methylation status had favorite results compared with high-risk human papillomavirus (hrHPV) testing. This validation trial evaluated the DNA methylation status and genotyping of hrHPV in unselected patients with gynecologic diseases.Methods This study enrolled all patients in the study center from June 1, 2019 to September 1, 2019. Liquid-based samples were collected from cervical swabs for methylation assays and hrHPV testing one day before surgery. The primary endpoint was the diagnostic accuracies of DNA methylation and hrHPV genotyping for cervical intraepithelial neoplasia (CIN) 2 or more severe lesions (CIN2+).Results In total, 307 patients were included in the final analysis, with a median age of 46 years. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the methylation assay for CIN2+ were 68.7%, 96.7%, 0.933 and 0.712, respectively, and the methylation assay achieved similar diagnostic accuracies to those in the training set and to hrHPV testing. Even in patients with negative hrHPV results, DNA methylation was significantly able to identify CIN2+ (odds ratio 39.857, 95% confidence interval 7.137-222.577). The methylation assay was sensitive for CIN2/3 and cervical squamous cell carcinoma without residual lesions and was not positive in this context.Conclusion For the diagnosis of cervical adenocarcinoma, methylation assessment, hrHPV testing and their combination had favorable results in all subtypes.

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High methylation of ZNF582 in cervical adenocarcinoma affects radiosensitivity and prognosis

Cited by 18 publications

References 30 publications

LncRNA ZNF582-AS1 Expression and Methylation in Breast Cancer and Its Biological and Clinical Implications

LncRNA ZNF582-AS1 Expression and Methylation in Breast Cancer and Its Biological and Clinical Implications

Methylation of PAX1 gene promoter in the prediction of concurrent chemo-radiotherapy efficacy in cervical cancer

DNA methylation for cervical cancer screening: A validation trial in China

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