scholarly journals SOX14 hypermethylation as a tumour biomarker in cervical cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jing Zhao ◽  
Huiling Cao ◽  
Wenfan Zhang ◽  
Yongjuan Fan ◽  
Shujuan Shi ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Intraepithelial Neoplasia ◽  
Cervical Squamous Cell Carcinoma ◽  
Pooled Analysis ◽  
The Cancer Genome Atlas ◽  
Diagnostic Efficacy ◽  
Normal Tissues ◽  
Methylation Specific Pcr ◽  
Specific Pcr ◽  
Positive Rate

Abstract Background The association between SOX14 and cancer has been reported. The aim of this study was to identify and validate the potential value of SOX14 methylation in the early detection of cervical cancer. Methods First, we extracted the data for SOX14 methylation and expression within cervical cancer from The Cancer Genome Atlas (TCGA) database and analysed them via UALCAN, Wanderer, MEXPRESS and LinkedOmics. Subsequently, according to the bioinformatics findings, primers and probes were designed for the most significantly differentiated methylation CpG site and synthesized for methylation-specific PCR (MSP) and quantitative methylation-specific PCR (QMSP) to verify SOX14 methylation in both cervical tissuses and liquid-based cell samples. Eventually, the clinical diagnostic efficacy of SOX14 methylation in the normal, cervical intraepithelial neoplasia, and cancer groups was analysed by ROCAUC. Results Pooled analysis demonstrated that SOX14 methylation levels were significantly increased in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) compared to normal tissues (P < 0.001). Both the verification and validation cohorts indicated that the methylation level and the positive rate of SOX14 gradually increased with increasing severity from normal to cancer samples (P < 0.01). When the cut-off value was set as 128.45, the sensitivity and specificity of SOX14 hypermethylation in the diagnosis of cervical cancer were 94.12 and 86.46%, respectively. When taken as a screening biomarker (>CINII), the sensitivity was 74.42% and the specificity was 81.48%, with a cut-off value of 10.37. Conclusion SOX14 hypermethylation is associated with cervical cancer and has the potential to be a molecular biomarker for the screening and early diagnosis of cervical cancer.

scholarly journals The Identification and Validation of EphA7 Hypermethylation, a Novel Biomarker, in Cervical Cancer

2021 ◽  
Author(s):  
Wenfan Zhang ◽  
Huiling Cao ◽  
Jing Zhao ◽  
Jinhao Yang ◽  
Zheng Liang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Dna Methylation ◽  
Aberrant Methylation ◽  
Clinical Value ◽  
Normal Tissues ◽  
Potential Value ◽  
Methylation Specific Pcr ◽  
Specific Pcr ◽  
Potential Biomarker ◽  
Positive Rate

Abstract Background Aberrant methylation of EphA7 has been reported in the process of carcinogenesis,but not including cervical cancer.Therefore,an integration study was performed to explore the association between EphA7 hypermethylation and cervical cancer and validate the potential value of EphA7 hypermethylation in the diagnosis of cervical cancer. Results Here, we performed an integration study to identify and validate the association between EphA7 methylation and cervical cancer. First, data on EphA7 methylation and expression in cervical cancer were extracted and analyzed via bioinformatics tools. The results showed that EphA7 promoter methylation levels were significantly increased in cervical cancer compared to normal tissues (P<0.001) and negatively correlated with EphA7 expression. Subsequently, these prediction results were confirmed in cell lines; moreover, CRISPR-based methylation perturbation tools (dCas9-Tet1/DNMT3a) were constructed to further demonstrate that DNA methylation participates in the regulation of EphA7 expression directly. Ultimately, the clinical value of EphA7 methylation in cervical cancer was validated in cervical tissues and Thinprep cytologic test (TCT) samples by methylation-specific PCR (MSP) and quantitative methylation-specific PCR (QMSP), respectively. Consistently, the methylation level and the positive rate of EphA7 gradually increased with severity from normal to cancer stages in TCT samples (P<0.01). Conclusion Above all, EphA7 presents hypermethylation in the cervical cancer,which is a potential biomarker in the diagnosis of cervical cancer.

Methylation in the Promoters of HS3ST2 and CCNA1 Genes is Associated with Cervical Cancer in Uygur Women in Xinjiang

2014 ◽  
Vol 29 (4) ◽  
pp. 354-362 ◽  
Author(s):  
Qiangqiang Zuo ◽  
Weinan Zheng ◽  
Jinli Zhang ◽  
Zemin Pan ◽  
Yinyin Liu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Invasive Cervical Cancer ◽  
Intraepithelial Neoplasia ◽  
Rt Pcr ◽  
Normal Tissues ◽  
Reverse Transcription Pcr ◽  
Specific Pcr ◽  
Cancer Tissues ◽  
Intraepithelial Lesions ◽  
Hypermethylated Genes

We assessed the suitability of HS3ST2 and CCNA1 genes as biomarkers for the early detection of cervical cancer in Uygur women in Xinjiang, China. Methylation-specific PCR (MSP) and HPV (HPV16 and HPV18)–specific PCR were performed on 110 cervical samples: 40 normal cervices, 10 cervical intraepithelial neoplasia 1 (CIN1), 10 CIN2, 10 CIN3 and 40 cervical cancer tissues. The expression of the 2 genes was measured by reverse transcription PCR (RT-PCR) in 10 methylation-positive and 10 methylation-negative cervical tissues. We found that both HS3ST2 and CCNA1 genes were methylated in 38 of the 40 cervical cancer tissues, 9 of the 10 CIN3, and 6 of the 10 CIN2. In contrast, methylation of these 2 genes was found in only 1 of the 40 normal tissues and none of 10 CIN1. Furthermore, hypermethylated HS3ST2 and CCNA1 genes were correlated with infection with HPV16 and HPV18 in high-grade squamous intraepithelial lesions (HSILs) and cervical cancer (both p<0.05). The expression of HS3ST2 and CCNA1 genes was lower in the methylation-positive cervical tissues than in the methylation-negative cervical tissues. Our results indicate that HS3ST2 and CCNA1 genes may play important roles in HPV-induced cervical cancer and that patients with specific hypermethylated genes may have a greater risk of progressing to invasive cervical cancer.

SUV39H1-Mediated DNMT1 is Participated in the Epigenetic Regulation of Smad3 in Cervical Cancer

2020 ◽  
Vol 20 ◽  
Author(s):  
Li Zhang ◽  
Sijuan Tian ◽  
Minyi Zhao ◽  
Ting Yang ◽  
Shimin Quan ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Lines ◽  
Epigenetic Regulation ◽  
Promoter Region ◽  
Methylation Status ◽  
Regulation Mechanism ◽  
Methylation Specific Pcr ◽  
Specific Pcr ◽  
Immune Factor ◽  
Cancer Tissues

Background: Smad3 is a pivotal intracellular mediator for participating in the activation of multiple immune signal pathway. Objective: The epigenetic regulation mechanism of the positive immune factor Smad3 in cervical cancer remains unknown. Therefore, the epigenetic regulation on Smad3 is investigated in this study. Methods: The methylation status of SMAD3 was detected by Methylation-specific PCR (MS-PCR) and Quantitative Methylation-specific PCR (MS-qPCR) in cervical cancer tissues and cell lines. The underlying molecular mechanisms of SUV39H1-DNMT1-Smad3 regulation was elucidated using cervical cancer cell lines containing siRNA or/and overexpression system. Confirmation of the regulation of DNMT1 by SUV39H1 used Chromatin immunoprecipitation-qPCR (ChIP-qPCR). The statistical methods used for comparing samples between groups were paired t tests and one-way ANOVAs. Results: H3K9me3 protein which regulated by SUV39H1 directly interacts with the DNMT1 promoter region to regulate its expression in cervical cancer cells, resulting in the reduce expression of the downstream target gene DNMT1. In addition, DNMT1 mediates the epigenetic modulation of the SMAD3 gene by directly binding to its promoter region. The depletion of DNMT1 effectively restores the expression of Smad3 in vitro. Moreover, in an in vivo assay, the expression profile of SUV39H1-DNMT1 was found to correlate with Smad3 expression in accordance with the expression at the cellular level. Notably, the promoter region of SMAD3 was hypermethylated in cervical cancer tissues, and this hypermethylation inhibits the subsequent gene expression. Conclusion: These results indicate that SUV39H1-DNMT1 is a crucial Smad3 regulatory axis in cervical cancer. SUV39H1-DNMT1 axis may provide a potential therapeutic target for the treatment of cervical cancer.

scholarly journals Oncogenic role of ALX3 in cervical cancer cells through KDM2B-mediated histone demethylation of CDC25A

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jinhong Qi ◽  
Li Zhou ◽  
Dongqing Li ◽  
Jingyuan Yang ◽  
He Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Cervical Squamous Cell Carcinoma ◽  
Cycle Progression ◽  
Normal Tissues ◽  
Positive Regulator ◽  
Cervical Cancer Cells

Abstract Background Cell division cycle 25A (CDC25A) is a well-recognized regulator of cell cycle progression and is involved in cancer development. This work focused on the function of CDC25A in cervical cancer cell growth and the molecules involved. Methods A GEO dataset GSE63514 comprising data of cervical squamous cell carcinoma (CSCC) tissues was used to screen the aberrantly expressed genes in cervical cancer. The CDC25A expression in cancer and normal tissues was predicted in the GEPIA database and that in CSCC and normal cells was determined by RT-qPCR and western blot assays. Downregulation of CDC25A was introduced in CSCC cells to explore its function in cell growth and the cell cycle progression. The potential regulators of CDC25A activity and the possible involved signaling were explored. Results CDC25A was predicted to be overexpressed in CSCC, and high expression of CDC25A was observed in CSCC cells. Downregulation of CDC25A in ME180 and C33A cells reduced cell proliferation and blocked cell cycle progression, and it increased cell apoptosis. ALX3 was a positive regulator of CDC25A through transcription promotion. It recruited a histone demethylase, lysine demethylase 2B (KDM2B), to the CDC25A promoter, which enhanced CDC25A expression through demethylation of H3k4me3. Overexpression of ALX3 in cells blocked the inhibitory effects of CDC25A silencing. CDC25A was found as a positive regulator of the PI3K/Akt signaling pathway. Conclusion This study suggested that the ALX3 increased CDC25A expression through KDM2B-mediated demethylation of H3K4me3, which induced proliferation and cell cycle progression of cervical cancer cells.

Screening of cervical cancer-related hub genes based on comprehensive bioinformatics analysis

2021 ◽  
pp. 1-13
Author(s):  
Simei Tu ◽  
Hao Zhang ◽  
Xiaocheng Yang ◽  
Wen Wen ◽  
Kangjing Song ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cervical Cancer ◽  
Molecular Mechanisms ◽  
Disease Free Survival ◽  
The Cancer Genome Atlas ◽  
Mrna Levels ◽  
Hub Genes ◽  
Normal Tissues ◽  
Significant Difference ◽  
Core Genes

BACKGROUND: Since the molecular mechanisms of cervical cancer (CC) have not been completely discovered, it is of great significance to identify the hub genes and pathways of this disease to reveal the molecular mechanisms of cervical cancer. OBJECTIVE: The study aimed to identify the biological functions and prognostic value of hub genes in cervical cancer. METHODS: The gene expression data of CC patients were downloaded from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. The core genes were screened out by differential gene expression analysis and weighted gene co-expression network analysis (WGCNA). R software, the STRING online tool and Cytoscape software were used to screen out the hub genes. The GEPIA public database was used to further verify the expression levels of the hub genes in normal tissues and tumour tissues and determine the disease-free survival (DFS) rates of the hub genes. The protein expression of the survival-related hub genes was identified with the Human Protein Atlas (HPA) database. RESULTS: A total of 64 core genes were screened, and 10 genes, including RFC5, POLE3, RAD51, RMI1, PALB2, HDAC1, MCM4, ESR1, FOS and E2F1, were identified as hub genes. Compared with that in normal tissues, RFC5, POLE3, RAD51,RMI1, PALB2, MCM4 and E2F1 were all significantly upregulated in cervical cancer, ESR1 was significantly downregulated in cervical cancer, and high RFC5 expression in CC patients was significantly related to OS. In the DFS analysis, no significant difference was observed in the expression level of RFC5 in cervical cancer patients. Finally, RFC5 protein levels verified by the HPA database were consistently upregulated with mRNA levels in CC samples. CONCLUSIONS: RFC5 may play important roles in the occurrence and prognosis of CC. It could be further explored and validated as a potential predictor and therapeutic target for CC.

scholarly journals CADM1, MAL and miR124-2 methylation analysis in cervical scrapes to detect cervical and endometrial cancer

2014 ◽  
Vol 67 (12) ◽  
pp. 1067-1071 ◽  
Author(s):  
Lise M A De Strooper ◽  
Marjolein van Zummeren ◽  
Renske D M Steenbergen ◽  
Maaike C G Bleeker ◽  
Albertus T Hesselink ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Dna Methylation ◽  
Endometrial Cancer ◽  
Gene Promoter ◽  
Intraepithelial Neoplasia ◽  
Promoter Hypermethylation ◽  
Methylation Analysis ◽  
Cervical Intraepithelial Neoplasia Grade ◽  
Specific Pcr ◽  
Dna Methylation Analysis

AimsGene promoter hypermethylation is recognised as an essential early step in carcinogenesis, indicating important application areas for DNA methylation analysis in early cancer detection. The current study was set out to assess the performance of CADM1, MAL and miR124-2 methylation analysis in cervical scrapes for detection of cervical and endometrial cancer.MethodsA series of cervical scrapes of women with cervical (n=79) or endometrial (n=21) cancer, cervical intraepithelial neoplasia grade 3 (CIN3) (n=16) or CIN2 (n=32), and women without evidence of CIN2 or worse (n=120) were assessed for methylation of CADM1, MAL and miR124-2. Methylation analysis was done by the PreCursor-M assay, a multiplex quantitative methylation-specific PCR.ResultsAll samples of women with cervical cancer (79/79, 100%), independent of the histotype, and 76% (16/21; 95% CI 58.0% to 94.4%) of women with endometrial cancer scored positive for DNA methylation for at least one of the three genes. In women without cancer, methylation frequencies increased significantly with severity of disease from 19.2% (23/120; 95% CI 12.1% to 26.2%) in women without CIN2 or worse to 37.5% (12/32; 95% CI 20.7% to 54.3%) and 68.8% (11/16; 95% CI 46.0% to 91.5%) in women with CIN2 and CIN3, respectively. Overall methylation positivity and the number of methylated genes increased proportionally to the lesion severity.ConclusionsDNA methylation analysis of CADM1, MAL and miR124-2 in cervical scrapes consistently detects cervical cancer and the majority of CIN3 lesions, and has the capacity to broaden its use on cervical scrapes through the detection of a substantial subset of endometrial carcinomas.

scholarly journals Integrative analysis of DNA methylation and gene expression identified cervical cancer-specific diagnostic biomarkers

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Wanxue Xu ◽  
Mengyao Xu ◽  
Longlong Wang ◽  
Wei Zhou ◽  
Rong Xiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cervical Cancer ◽  
Dna Methylation ◽  
Regulation Of Gene Expression ◽  
Cervical Squamous Cell Carcinoma ◽  
Integrative Analysis ◽  
Machine Learning Techniques ◽  
Marker Genes ◽  
Normal Tissues ◽  
Candidate Set

AbstractCervical cancer is the leading cause of death among women with cancer worldwide. Here, we performed an integrative analysis of Illumina HumanMethylation450K and RNA-seq data from TCGA to identify cervical cancer-specific DNA methylation markers. We first identified differentially methylated and expressed genes and examined the correlation between DNA methylation and gene expression. The DNA methylation profiles of 12 types of cancers, including cervical cancer, were used to generate a candidate set, and machine-learning techniques were adopted to define the final cervical cancer-specific markers in the candidate set. Then, we assessed the protein levels of marker genes by immunohistochemistry by using tissue arrays containing 93 human cervical squamous cell carcinoma samples and cancer-adjacent normal tissues. Promoter methylation was negatively correlated with the local regulation of gene expression. In the distant regulation of gene expression, the methylation of hypermethylated genes was more likely to be negatively correlated with gene expression, while the methylation of hypomethylated genes was more likely to be positively correlated with gene expression. Moreover, we identified four cervical cancer-specific methylation markers, cg07211381 (RAB3C), cg12205729 (GABRA2), cg20708961 (ZNF257), and cg26490054 (SLC5A8), with 96.2% sensitivity and 95.2% specificity by using the tenfold cross-validation of TCGA data. The four markers could distinguish tumors from normal tissues with a 94.2, 100, 100, and 100% AUC in four independent validation sets from the GEO database. Overall, our study demonstrates the potential use of methylation markers in cervical cancer diagnosis and may boost the development of new epigenetic therapies.

scholarly journals Identification of Core Genes Involved in the Progression of Cervical Cancer Using an Integrative mRNA Analysis

2020 ◽  
Vol 21 (19) ◽  
pp. 7323
Author(s):  
Marina Dudea-Simon ◽  
Dan Mihu ◽  
Alexandru Irimie ◽  
Roxana Cojocneanu ◽  
Schuyler S. Korban ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Molecular Mechanisms ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Normal Tissues ◽  
High Incidence ◽  
Cancer Genome Atlas ◽  
Mrna Analysis ◽  
Core Genes ◽  
Significant Mortality

In spite of being a preventable disease, cervical cancer (CC) remains at high incidence, and it has a significant mortality rate. Although hijacking of the host cellular pathway is fundamental for developing a better understanding of the human papillomavirus (HPV) pathogenesis, a major obstacle is identifying the central molecular targets involved in HPV-driven CC. The aim of this study is to investigate transcriptomic patterns of HPV-infected and normal tissues to identify novel prognostic markers. Analyses of functional enrichment and interaction networks reveal that altered genes are mainly involved in cell cycle, DNA damage, and regulated cell-to-cell signaling. Analysis of The Cancer Genome Atlas (TCGA) data has suggested that patients with unfavorable prognostics are more likely to have DNA repair defects attributed, in most cases, to the presence of HPV. However, further studies are needed to fully unravel the molecular mechanisms of such genes involved in CC.

Exploring an Appropriate Method of Cervical Cancer Screening in Rural China

2019 ◽  
Vol 31 (7) ◽  
pp. 652-658 ◽  
Author(s):  
Xiaosong Zhang ◽  
Gengli Zhao ◽  
Hui Bi ◽  
Min Zhou ◽  
Xueyin Wang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Screening ◽  
Cervical Cancer Screening ◽  
Rural Areas ◽  
Detection Rate ◽  
Rural China ◽  
Intraepithelial Neoplasia ◽  
Screening Strategy ◽  
Significant Difference ◽  
Positive Rate

Background. To explore the feasibility of careHPV (human papillomavirus) with cytology triage as a cervical cancer screening in rural areas of China. Methods. A total of 7138 women aged 35 to 64 years were divided into 2 groups. Women in careHPV group (n = 3536) underwent careHPV and 288 positive subjects underwent cytology, of which 65 women were ≥ASC-US (atypical squamous cells of undetermined significance). Women in the cytology group (n = 3602) underwent cytology and 111 women were ≥ASC-US. All subjects with ≥ASC-US were referred to colposcopy and biopsy. Results. The average age of subjects was 48.2 ± 7.8 years. In the careHPV group, the HPV-positive rate was 8.1%. The detection rate of ≥ASC-US was 1.8% in the careHPV group and 3.1% in the cytology group ( P = .001). There was no significant difference in detection rate of ≥CINII (cervical intraepithelial neoplasia) in the careHPV group (0.7%) and the cytology group (0.6%; P = .416). In addition, to identify 1 case ≥CINII, an average of 2.6 colposcopies were needed in the careHPV group, and 5.3 colposcopies were performed to diagnose 1 case ≥CINII in the cytology group. Conclusions. careHPV with cytology triage offered similar efficiency in identifying abnormalities of CINII and above compared with cytology screening. With the reduced requirement for cytology testing and colposcopy, careHPV may be a more favorable cervical cancer screening strategy in areas of China where there is a lack of cytology services.

scholarly journals Expressions of sFRP1 and β-Catenin in Cervical Cancer

2012 ◽  
Vol 31 (1) ◽  
pp. 6-11 ◽  
Author(s):  
Xiao-yan Zhang ◽  
Lin Wang ◽  
Yuhuan Qiao ◽  
Ruixia Guo
Keyword(s):  
Cervical Cancer ◽  
Survival Rate ◽  
Lymphatic Metastasis ◽  
Intraepithelial Neoplasia ◽  
Clinicopathological Characteristics ◽  
Related Protein ◽  
Sfrp1 Expression ◽  
Protein Expressions ◽  
Positive Rate ◽  
The Relationship

Expressions of sFRP1 and β-Catenin in Cervical Cancer This study aimed to investigate the expressions of secreted frizzled-related protein 1 (sFRP1) and β-catenin in cervical cancer and cervical intraepithelial neoplasia (CIN), and to explore the relationship between both proteins and the prognosis of cervical cancer. Immunohistochemistry was performed to detect the protein expressions of sFRP1 and β-catenin in cervical cancer (n=78), CIN (n=30) and normal cervical tissues (n=20), and the relationships of sFRP1 and β-catenin with the clinicopathological characteristics and prognosis of cervical cancer were analyzed. The positive rate of sFRP1 was 100%, 70% and 33.3% in the normal cervical tissues, CIN and cervical cancer, respectively (P<0.05). The sFRP1 expression was positively correlated with the stage of cervical cancer and lymphatic metastasis (P<0.05). The 5-year survival rate was significantly higher in patients positive for sFRP1 than in those negative for sFRP1 (P<0.05). The rate of abnormal β-catenin expression in the normal cervical tissues, CIN and cervical cancer was 5%, 43.3% and 70.5%, respectively (P<0.05). The abnormal β-catenin expression was positively correlated with the stage of cervical cancer, lymphatic metastasis and pathological grade (P<0.05). The 5-year survival rate was markedly higher in patients with normal β-catenin expression than in those with abnormal β-catenin expression (P<0.05). The sFRP1 expression was negatively related to the β-catenin expression in cervical cancer (r = -0.557, P<0.001). Both sFRP1 and β-catenin play important roles in the initiation and development of cervical cancer, and both proteins can be used as indicators predicting the prognosis of cervical cancer.

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