scholarly journals Effect of LHX2 gene methylation level and its function on radiotherapy of cervical cancer

2021 ◽  
Vol 0 (0) ◽  
pp. 0-0
Author(s):  
Rong Yu ◽  
Lihe Zhang ◽  
Qin Yu ◽  
Haiping Zhao ◽  
Hao Yang ◽  
...  
2020 ◽  
Author(s):  
Chunhe Zhang ◽  
Shaowei Fu ◽  
Luyue Wang ◽  
Fang Wang ◽  
Dan Wu ◽  
...  

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.


2016 ◽  
Author(s):  
Rafael Guerrero-Preston ◽  
Anne Jedlicka ◽  
Blanca L. Valle ◽  
Nitesh Turaga ◽  
Liliana Florea ◽  
...  

2017 ◽  
Vol 27 (7) ◽  
pp. 1480-1488 ◽  
Author(s):  
Ting Luan ◽  
Quan Hua ◽  
Xia Liu ◽  
Pengfei Xu ◽  
Yun Gu ◽  
...  

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.


Author(s):  
Jinpu Cai ◽  
Yuyang Xu ◽  
Wen Zhang ◽  
Shiying Ding ◽  
Yuewei Sun ◽  
...  

Abstract Motivation: DNA methylation is a biological process impacting the gene functions without changing the underlying DNA sequence. The DNA methylation machinery usually attaches methyl groups to some specific cytosine residues, which modify the chromatin architectures. Such modifications in the promoter regions will inactivate some tumor-suppressor genes. DNA methylation within the coding region may significantly reduce the transcription elongation efficiency. The gene function may be tuned through some cytosines are methylated. Methods: This study hypothesizes that the overall methylation level across a gene may have a better association with the sample labels like diseases than the methylations of individual cytosines. The gene methylation level is formulated as a regression model using the methylation levels of all the cytosines within this gene. A comprehensive evaluation of various feature selection algorithms and classification algorithms is carried out between the gene-level and residue-level methylation levels. Results: A comprehensive evaluation was conducted to compare the gene and cytosine methylation levels for their associations with the sample labels and classification performances. The unsupervised clustering was also improved using the gene methylation levels. Some genes demonstrated statistically significant associations with the class label, even when no residue-level methylation features have statistically significant associations with the class label. So in summary, the trained gene methylation levels improved various methylome-based machine learning models. Both methodology development of regression algorithms and experimental validation of the gene-level methylation biomarkers are worth of further investigations in the future studies. The source code, example data files and manual are available at http://www.healthinformaticslab.org/supp/.


Author(s):  
Suzanna P Mongan ◽  
Andrijono Andrijono ◽  
Hartono Tjahadi

Objective: To determine whether HPV L1 gene methylation can be used in triage of precancerous cervical lesions. The main objective is to determine the genotype of HPV in cervical precancerous lesions and to determine the percentage, the sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio of DNA HPV L1 methylation in precancerous cervical lesions. Methods: A number of 57 samples of paraffin blocks (FFPE) from precancerous lesions and cervical cancer biopsies in the Department of Pathology Faculty of Medicine-Cipto Mangunkusumo General Hospital that had been re-evaluated by the pathologist, underwent extraction of HPV DNA. The genotypes of HPV DNA were examined using primers GP5 / 6 and specific HPV 16, HPV 18 and HPV 52 probes and analyzed by real time PCR. Sequencing was performed on samples with unknown HPV DNA type that were detected using the specific probes to determine the type of HPV. Bisulfite conversion procedure was then performed for the samples that met the inclusion criteria. Results: There were 30 samples (52.6%) with CIN 1, 12 samples (21.1%) CIN 2, 9 samples (15.8%) CIN 3 and 6 samples (10.5%) of cervical cancer. Most of the samples were 36-45 years (35.1%). Of the total 57 samples, 55 samples were successfully extracted and determined the DNA genotyping of HPV (96.5%). HPV 16 infections both in the form of single or multiple was found to be 76.36%. The samples were mostly dominated by co-infection of HPV16 and 18 (49.1%) followed by HPV 16 (24.6%) and HPV 18 (14.0%). Based on the sequencing results there were other types of high risk HPV infection found: HPV 33, HPV 35, HPV 58 and also undeterminate risk HPV 53 and low risk HPV 54. After several procedures of optimization for methylation examination of HPV DNA L1 there was thin band found in electrophoresis procedure in 8 of 42 samples (19%) of HPV 16 after bisulfite conversion but once it was purified there weren’t any band found so we can not proceed to the stage sequencing. Until now we are still in the stage of optimizing the methylation procedure. Conclusion: HPV 16 infection were most commonly found in the form of single or multiple. Co-infection of HPV 16 and 18 were found in the majority of the samples. There were no significant correlation between HPV type and the severity of cervical lesions. Until now, the examination of DNA methylation HPV L1 already obtained eight samples of HPV 16 with a thin band on electrophoresis but the result could not be concluded because it is still in the process of optimization. [Indones J Obstet Gynecol 2017; 5-2: 120-126] Keywords: HPV DNA genotype, L1 gene methylation, precancerous cervical lesions


2021 ◽  
Vol Volume 14 ◽  
pp. 403-411
Author(s):  
Chunhe Zhang ◽  
Shaowei Fu ◽  
Luyue Wang ◽  
Fang Wang ◽  
Dan Wu ◽  
...  

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4497-4497
Author(s):  
Bao-An Chen ◽  
Bei-ming Shou ◽  
Dong-rui Zhou ◽  
Delong Liu ◽  
Jia-hua Ding ◽  
...  

Abstract Objective Aberrant DNA methylation of CpG site is among the earliest and most frequent alterations in cancer. The aim of this study was to study whether phenylhexyl isothiocyanate can reduce the methylation level of P16 gene. This study used a microarray-based method for quantificationally detecting changes of P16 gene methylation in leukemia patient and U266 cell line. And to simply discuss the effect of phenylhexyl isothiocyanate on tumor methylation. Methods This method used bisulfite-modified DNA as a template for PCR amplification, resulting in conversion of unmethylated cytosine, but not methylated cytosine, into thymine within CpG islands of interest. One set of oligonucleotide probes were designed to fabricate a DNA microarray to detect the methylation changes of P16 gene CpG islands. Each set contained a pair of methylated and unmethylated oligonucleotides for interrogating 3 CpG sites in close proximity. By TA cloning, PCR, sequencing, positive and negative DNA targets were required. Next drawing a standard curve by fluorescence intensity. Leukemia samples DNA were abstracted and bisulfite-modified. Sample DNA targets were required by PCR amplification and were hybridized with the microarry. Finally the microarry was scanned with ScanArray Lite microarray analysis systems. Results The linear relationship (R2=0.9660) was established and it could be used to eliminate background noise. The methylation level of U266 is hypermethylation, after cultured with PHI, the level reduce. Eleven patients have P16 gene hypermethylation in thrity. After culture with PHI, seven patients showed level reduce, one patient showed raise, three patients showed remaining. Conclusion PHI can reduce the methylation level of P16 gene in U266 cell line, and also can reduce the methylation level of P16 gene of leukemia patient samples in vitro culture.


2016 ◽  
Vol 75 (11) ◽  
pp. 1998-2006 ◽  
Author(s):  
Ming Zhao ◽  
Yin Zhou ◽  
Bochen Zhu ◽  
Mengjie Wan ◽  
Tingting Jiang ◽  
...  

ObjectiveSystemic lupus erythematosus (SLE) is a clinically heterogeneous disease with limited reliable diagnostic biomarkers. We investigated whether gene methylation could meet sensitivity and specificity criteria for a robust biomarker.MethodsIFI44L promoter methylation was examined using DNA samples from a discovery set including 377 patients with SLE, 358 healthy controls (HCs) and 353 patients with rheumatoid arthritis (RA). Two independent sets including 1144 patients with SLE, 1350 HCs, 429 patients with RA and 199 patients with primary Sjögren's syndrome (pSS) were used for validation.ResultsSignificant hypomethylation of two CpG sites within IFI44L promoter, Site1 (Chr1: 79 085 222) and Site2 (Chr1: 79 085 250; cg06872964), was identified in patients with SLE compared with HCs, patients with RA and patients with pSS. In a comparison between patients with SLE and HCs included in the first validation cohort, Site1 methylation had a sensitivity of 93.6% and a specificity of 96.8% at a cut-off methylation level of 75.5% and Site2 methylation had a sensitivity of 94.1% and a specificity of 98.2% at a cut-off methylation level of 25.5%. The IFI44L promoter methylation marker was also validated in an European-derived cohort. In addition, the methylation levels of Site1 and Site2 within IFI44L promoter were significantly lower in patients with SLE with renal damage than those without renal damage. Patients with SLE showed significantly increased methylation levels of Site1 and Site2 during remission compared with active stage.ConclusionsThe methylation level of IFI44L promoter can distinguish patients with SLE from healthy persons and other autoimmune diseases, and is a highly sensitive and specific diagnostic marker for SLE.


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