Study on the Expression and Significance of P16 Gene Methylation Based on Information Technology Statistics in Female Cervical Cancer in Hunan Povince

Abstract Background This study aimed to determine whether ZNF582 gene methylation and tissue protein expression can be used as a tool with high sensitivity and specificity for cervical cancer screening. We analyzed the correlation between promoter methylation of the zinc finger protein 582 (ZNF582) gene and cervical cancer and high risk HPV16/18 infection. Methods Tissue samples of normal cervical or chronic cervicitis (n=51), CIN (cervical intraepithelial neoplasia) (n=35), and cervical carcinoma (n=68) were tested for HPV16/18 infection by polymerase chain reaction (PCR). We also detected the methylation status of the ZNF582 gene promoter in the same tissues by methylation specific PCR (MSP), then analyzed the correlation between ZNF582 promoter methylation and HPV16/18 infection. Immunohistochemistry was used to analyze ZNF582 gene expression in 152 cervical tissues. We detected ZNF582 mRNA expression in cervical tissues (including cancer and non-cancer) by real-time fluorescence quantitative PCR (qRT-PCR).Results Among 93 high grade cervical lesions (CINII and above) and cervical cancer samples, 57 cases were positive for HPV16/18 infection and 36 cases were negative. ZNF582 gene methylation occurred in 9 out of 51 cases in normal cervical tissues (17.6%), 16 of 35 cases in CIN tissues (45.7%), and 50 of 68 cases in cervical cancer (73.5%). The differences in methylation rate of the three groups were statistically significant (P<0.05). The ZNF582 methylation rate in the positive HPV16/18 infection group was 73.7%, while the negative group was 63.9%. Compared with normal tissues, ZNF582 protein was highly expressed in cervical cancer tissues, but mRNA expression was low.Conclusion While ZNF582 protein is highly expressed in cervical cancer tissues, it was not sufficient for use as a standard for cervical cancer staging. On the other hand, ZNF582 promoter methylation had high specificity and sensitivity in detecting CINII and highly diseased cervical lesions and could be used as a diagnostic marker for cervical cancer of women.

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Promoter Methylation of p16 Gene in Cervical Cancer

Korean Journal of Gynecologic Oncology ◽

10.3802/kjgo.2005.16.1.21 ◽

2005 ◽

Vol 16 (1) ◽

pp. 21

Author(s):

Dae Hoon Jeong ◽

Mi Young Youm ◽

Hyun Kyung Park ◽

Young Nam Kim ◽

Kyung Bok Lee ◽

...

Keyword(s):

Cervical Cancer ◽

Promoter Methylation ◽

P16 Gene

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The application value of PAX1 and ZNF582 gene methylation in high grade intraepithelial lesion and cervical cancer

Clinical & Translational Oncology ◽

10.1007/s12094-020-02416-5 ◽

2020 ◽

Author(s):

H. Liang ◽

G. L. Li ◽

J. Liu ◽

M. Fu ◽

H. Huang ◽

...

Keyword(s):

Cervical Cancer ◽

High Grade ◽

Gene Methylation ◽

Intraepithelial Lesion

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Abstract B11: Viral and host gene methylation in liquid prep: novel molecular screening and triage tools to reduce cervical cancer disparities

10.1158/1538-7755.disp15-b11 ◽

2016 ◽

Author(s):

Rafael Guerrero-Preston ◽

Anne Jedlicka ◽

Blanca L. Valle ◽

Nitesh Turaga ◽

Liliana Florea ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Disparities ◽

Host Gene ◽

Molecular Screening ◽

Gene Methylation

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PAX1 Methylation as a Potential Biomarker to Predict the Progression of Cervical Intraepithelial Neoplasia: A Meta-analysis of Related Studies

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000001011 ◽

2017 ◽

Vol 27 (7) ◽

pp. 1480-1488 ◽

Cited By ~ 5

Author(s):

Ting Luan ◽

Quan Hua ◽

Xia Liu ◽

Pengfei Xu ◽

Yun Gu ◽

...

Keyword(s):

Cervical Cancer ◽

Cervical Intraepithelial Neoplasia ◽

Web Of Science ◽

Meta Analysis ◽

Great Influence ◽

Intraepithelial Neoplasia ◽

Cochrane Library ◽

Gene Methylation ◽

Potential Biomarker ◽

Number Of Patients

ObjectiveThe methylation of paired box gene 1 (PAX1) has a great influence on the process of cervical lesion. However, available evidence for the association between PAX1 methylation and cervical intraepithelial neoplasia (CIN) are inconsistent. Here, we systematically reviewed and analyzed PAX1 methylation in progress of CIN.MethodsTwo investigators independently searched eligible studies of PAX1 methylation and CIN that were published in PubMed, Cochrane Library, EMBASE, and Web of Science databases until November 30, 2016. We extracted clinicopathologic features of CIN and cervical cancel relevant to PAX1 methylation. Odds ratios (ORs) with their 95% confidence intervals (CIs) were used to assess the association between PAX1 methylation and progression of patients with CIN.ResultsSeven studies composed of 1055 patients with various stages of CIN and cervical cancel were eventually included. The results revealed that PAX1 methylation was associated with transition of CIN I to CIN II/III (OR, 0.09; 95% CI, 0.04–0.19) and CIN II/III to cervical cancer (OR, 0.16; 95% CI, 0.05–0.46), and similar results were produced in sensitivity analysis. Also, we found that the OR value was associated with average age and number of patients, publication year, and study location of included articles.ConclusionsPAX1 gene methylation was associated with the transition of CIN I to CIN II/III and CIN II/III to cervical cancer, so that it could be an auxiliary biomarker to estimate the risk of CIN progress. Moreover, PAX1 may help to determine appropriate reexaminations and treatment for patients with various stages of CIN.

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Tumor suppressor p16 methylation in multiple myeloma: biological and clinical implications

Blood ◽

10.1182/blood-2006-05-024661 ◽

2006 ◽

Vol 109 (3) ◽

pp. 1228-1232 ◽

Cited By ~ 52

Author(s):

Natalia Gonzalez-Paz ◽

Wee J. Chng ◽

Rebecca F. McClure ◽

Emily Blood ◽

Martin M. Oken ◽

...

Keyword(s):

Multiple Myeloma ◽

Cell Labeling ◽

Clinical Implications ◽

Gene Methylation ◽

P16 Gene ◽

Specific Pcr ◽

Long Term Follow Up ◽

Clinical Consequences

Abstract The biological and clinical implications of p16 gene methylation in multiple myeloma (MM) are still unclear despite previous studies. In this comprehensive study, using methylation-specific PCR (MS-PCR), we show that p16 methylation is relatively common and occurs in monoclonal gammopathy of undetermined significance (MGUS; n = 17), smoldering multiple myeloma (SMM; n = 40), and MM (n = 522) at a prevalence of 24%, 28%, and 34%, respectively. However, p16 methylation does not appear to affect gene expression level. In a large cohort of patients with long-term follow-up information (n = 439), there was no difference in overall survival between patients with or without p16 methylation. We also found no association between p16 methylation and the main cytogenetic categories, although it was more common among patients with 17p13.1 deletions (p53 locus), a genetic progression event in MM. In addition, p16 methylation has no apparent effect on the cycle because there was also no difference in the plasma cell labeling index (a direct measurement of proliferation) between patients with and without p16 methylation. Our results question a major role for p16 methylation in the oncogenesis of the PC neoplasm, and we now believe p16 methylation may be a marker for overall epigenetic changes associated with disease progression, with no obvious direct biological or clinical consequences.

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Frequent aberrant methylation of p16INK4a in primary rat lung tumors.

Molecular and Cellular Biology ◽

10.1128/mcb.17.3.1366 ◽

1997 ◽

Vol 17 (3) ◽

pp. 1366-1374 ◽

Cited By ~ 101

Author(s):

D S Swafford ◽

S K Middleton ◽

W A Palmisano ◽

K J Nikula ◽

J Tesfaigzi ◽

...

Keyword(s):

Cell Lines ◽

Cpg Island ◽

Homozygous Deletion ◽

Lung Tumors ◽

Aberrant Methylation ◽

Rat Lung ◽

Small Cell Lung ◽

Gene Methylation ◽

P16 Gene ◽

Primary Tumors

The p16INK4a (p16) tumor suppressor gene is frequently inactivated by homozygous deletion or methylation of the 5' CpG island in cell lines derived from human non-small-cell lung cancers. However, the frequency of dysfunction in primary tumors appears to be significantly lower than that in cell lines. This discordance could result from the occurrence or selection of p16 dysfunction during cell culture. Alternatively, techniques commonly used to examine tumors for genetic and epigenetic alterations may not be sensitive enough to detect all dysfunctions within the heterogeneous cell population present in primary tumors. If p16 inactivation plays a central role in development of non-small-cell lung cancer, then the frequency of gene inactivation in primary tumors should parallel that observed in cell lines. The present investigation addressed this issue in primary rat lung tumors and corresponding derived cell lines. A further goal was to determine whether the aberrant p16 gene methylation seen in human tumors is a conserved event in this animal model. The rat p16 gene was cloned and sequenced, and the predicted amino acid sequence of its product found to be 62% homologous to the amino acid sequence of the human analog. Homozygous deletion accounted for loss of p16 expression in 8 of 20 cell lines, while methylation of the CpG island extending throughout exon 1 was observed in 9 of 20 cell lines. 2-Deoxy-5-azacytidine treatment of cell lines with aberrant methylation restored gene expression. The methylated phenotype seen in cell lines showed an absolute correlation with detection of methylation in primary tumors. Aberrant methylation was also detected in four of eight primary tumors in which the derived cell line contained a deletion in p16. These results substantiate the primary tumor as the origin for dysfunction of the p16 gene and implicate CpG island methylation as the major mechanism for inactivating this gene in the rat lung tumors examined. Furthermore, rat lung cancer appears to be an excellent model in which to investigate the mechanisms of de novo gene methylation and the role of p16 dysfunction in the progression of neoplasia.

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Methylation of p15 and p16 Genes in Acute Promyelocytic Leukemia: Potential Diagnostic and Prognostic Significance

Journal of Clinical Oncology ◽

10.1200/jco.2001.19.7.2033 ◽

2001 ◽

Vol 19 (7) ◽

pp. 2033-2040 ◽

Cited By ~ 71

Author(s):

C.S. Chim ◽

R. Liang ◽

C.Y.Y. Tam ◽

Y.L. Kwong

Keyword(s):

Acute Promyelocytic Leukemia ◽

Methylation Status ◽

Prognostic Significance ◽

Disease Free Survival ◽

Promyelocytic Leukemia ◽

Gene Methylation ◽

P16 Gene ◽

Potential Marker ◽

Disease Free

PURPOSE: To investigate the frequency of p15 and p16 gene promoter methylation in acute promyelocytic leukemia (APL), and to define its value in the detection of minimal residual disease (MRD) and treatment prognostication. PATIENTS AND METHODS: Bone marrow DNA obtained from 26 patients with APL at diagnosis and during follow-up was studied with the methylation-specific polymerase chain reaction (MS-PCR). Serial marrow DNA was studied by MS-PCR for MRD, and disease-free and overall survival were correlated with p15 methylation status at diagnosis. RESULTS: MS-PCR for p16 and p15 gene methylation has a maximum sensitivity of 10-4 and 10-5. At diagnosis, 19 patients (73.1%) exhibited p15 methylation, whereas only three patients (11.5%) exhibited p16 methylation, all of whom had concomitant p15 methylation. During follow-up, p16 methylation was acquired in two patients, one during the third hematologic relapse, and the other during transformation into therapy-related myelodysplastic syndrome. Six patients were evaluated serially with MS-PCR for p15 methylation at diagnosis and at follow-up examinations. Persistent p15 methylation preceded subsequent hematologic relapses in two patients, and conversion to negative MS-PCR for p15 methylation correlated with prolonged survival in another four patients. The 5-year disease-free survival of patients with p15 methylation was significantly inferior to that of patients without p15 methylation (15% v 62.5%; P = .02), and this remained significant in multivariate analysis. CONCLUSION: In APL, p15 but not p16 gene methylation is frequent. It is possible that p16 methylation is acquired during clonal evolution. p15 methylation is a potential marker of MRD and might be of prognostic significance.

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