Estrogen receptor promoter methylation predicts survival in low-grade ovarian carcinoma patients

Kirn, Verena; Shi, Rong; Heublein, Sabine; Knabl, Julia; Guenthner-Biller, Margit; Andergassen, Ulrich; Fridrich, C; Malter, Wolfram; Harder, Jan; Friese, Klaus; Mayr, Doris; Jeschke, Udo

doi:10.1007/s00432-014-1729-9

Cited by 11 publications

(8 citation statements)

References 24 publications

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“…Numerous studies have aimed to introduce new biological prognostic factors in ovarian cancer. Recently, carbohydrate stem cell marker TF1 has been proposed as negative prognostic marker in ovarian cancer displaying wildtype p53, while estrogen receptor promoter methylation could predict overall survival in low-grade ovarian carcinoma patients [5,6]. Although for these and various other molecules the prognostic value independently of clinical parameters has been proven, until today, except for breast cancer gene (BRCA)-status, no biological marker is commonly accepted [4].…”

Section: Introductionmentioning

confidence: 99%

Galectins-1, -3, and -7 Are Prognostic Markers for Survival of Ovarian Cancer Patients

Schulz

Schmoeckel

Kühn

et al. 2017

IJMS

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There is a tremendous need for developing new useful prognostic factors in ovarian cancer. Galectins are a family of carbohydrate binding proteins which have been suggested to serve as prognostic factors for various cancer types. In this study, the presence of Galectin-1, -3, and -7 was investigated in 156 ovarian cancer specimens by immunochemical staining. Staining was evaluated in the cytoplasm and nucleus of cancer cells as well as the peritumoral stroma using a semi quantitative score (Remmele (IR) score). Patients’ overall survival was compared between different groups of Galectin expression. Galectin (Gal)-1 and -3 staining was observed in the peritumoral stroma as well as the nucleus and cytoplasm of tumor cells, while Gal-7 was only present in the cytoplasm of tumor cells. Patients with Gal-1 expression in the cytoplasm or high Gal-1 expression in the peritumoral stroma showed reduced overall survival. Nuclear Gal-3 staining correlated with a better outcome. We observed a significantly reduced overall survival for cases with high Gal-7 expression and a better survival for Gal-7 negative cases, when compared to cases with low expression of Gal-7. We were able to show that both tumor and stroma staining of Gal-1 could serve as negative prognostic factors for ovarian cancer. We were able to confirm cytoplasmic Gal-7 as a negative prognostic factor. Gal-3 staining in the nucleus could be a new positive prognosticator for ovarian cancer.

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Section: Introductionmentioning

confidence: 99%

Galectins-1, -3, and -7 Are Prognostic Markers for Survival of Ovarian Cancer Patients

Schulz

Schmoeckel

Kühn

et al. 2017

IJMS

Self Cite

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“…Numerous studies have shown that PTEN, as a key link, is involved in the PI3K/AKT/PTEN drug-resistance pathway and participates in drug resistance in OC by affecting biological processes, such as DNA methylation, cell cycle, apoptosis, and cell proliferation. [ 11 , 20 – 22 ] In addition, it had been reported that changes in gene methylation of ESR1 [ 23 , 24 ] are involved in the development and drug resistance in OC and are associated with prognosis. With reference to MDM2 and CD44, although no previous studies have shown that changes in methylation are associated with OC and drug resistance in OC, numerous studies have indicated that both MDM2 and CD44 genes are involved in drug resistance in OC, and are related to the prognosis of OC.…”

Section: Resultsmentioning

confidence: 99%

“…[ 38 ] However, some studies have also shown that in low-grade serous ovarian cancer, the degree of methylation of the ESR1 promoter is negatively related to survival rate. [ 24 ] Another example is that ETS1 is a key regulator of the PARP1 gene in BRCA1 mutant ovarian cancer, and its degree of methylation is significantly associated with the prognosis of OC. [ 14 ] In addition, CD44-positive cells of OC are associated with poor prognosis of OC.…”

Section: Discussionmentioning

confidence: 99%

Big data-based identification of methylated genes associated with drug resistance and prognosis in ovarian cancer

et al. 2020

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It is imperative to further the understanding of the drug resistance mechanisms of ovarian cancer (OC) and to identify useful biological markers for prognosis prediction. Cormine, cBioportal, and The Cancer Genome Atlas databases were used to search microarray data of gene methylation related to OC, drug resistance in OC, and prognosis, and to analyze methylated genes potentially inducing the drug resistance in OC. Fifty-five DNA-methylated genes significantly associated with drug resistance in OC were screened, and the regulatory mechanisms underlying changes in methylation levels of these genes were systematically integrated. Enrichment and annotation of biological processes indicated that most of the above DNA-methylated genes were significantly associated with cell proliferation and cell cycle. In addition, pathway enrichment demonstrated that the above DNA-methylated genes were significantly associated with PI3K-AKT and P53 signaling pathways. Among the 55 genes, 4 were significantly associated with OC prognostic disease-free survival, namely bromodomain containing 4, PDZ domain containing 1 ( PDZK1) , phosphatase and tensin homolog, and TNF receptor superfamily member 10c; 5 were significantly related to overall survival, namely bromodomain containing 4, PDZK1 , PIK3C2B , Rh associated glycoprotein, and DYRK ; among them, the degree of methylation of TNF receptor superfamily member 10c, PDZK1 , and Rh associated glycoprotein genes was significantly correlated with mRNA expression. Furthermore, PDZK1 , Rh associated glycoprotein, and TNF receptor superfamily member 10c genes showed significant hypomethylation in drug-resistance tissues of OC, and their mRNAs had significantly high expression. The association between the methylation of these 55 genes and OC and drug resistance in OC, in addition to bioinformatics analyses clarify the important mechanisms of gene methylation in the development, progression, and drug resistance of OC.

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“…It is well known that loss of ESR in breast cancer patients indicates invasiveness and poor prognosis 28. In ovarian carcinoma, ESR1 methylation influences ovarian cancer development, and its promoter methylation was negatively correlated with survival in the subgroup of low-grade ovarian carcinoma patients 29…”

Section: Discussionmentioning

confidence: 99%

<p>Identification of candidate biomarkers correlated with the diagnosis and prognosis of cervical cancer via integrated bioinformatics analysis</p>

Dai

Chen

Wang

et al. 2019

OTT

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Background: Cervical carcinoma is one of the most common malignant gynecological tumors and is associated with high rates of morbidity and mortality. Early diagnosis and early treatment can reduce the mortality rate of cervical cancer. However, there is still no specific biomarkers for the diagnosis and detection of cervical cancer prognosis. Therefore, it is greatly urgent in searching biomarkers correlated with the diagnosis and prognosis of cervical cancer. Results: The mRNA and microRNA expression profile datasets (GSE7803, GSE9750, GSE63514, and GSE30656) were downloaded from the Gene Expression Omnibus database (GEO). The three microarray datasets were integrated to one via integrated bioinformatics. Differentially expressed genes (DEGs) and microRNAs (DEMs) were obtained by R software. The protein–protein interaction (PPI) networks of the DEGs were performed from the STRING database and further visualized by Cytoscape software. A total of 83 DEGs and 14 DEMs were screened from the microarray expression profile datasets. The miRNAs validated to be associated with cervical cancer were obtained using HMDD online website and the target genes of DEMs were identified using the miRWalk2.0 online database. ESR1, PPP1R3C, NSG1 , and TMPRSS11D were the gene targets of hsa-miR-21; the targets of hsa-miR-16 were GYS2, ENDOU , and KLF4 . These targets were all downregulated in cervical cancer. Finally, we verified the expression of those targets in cervical tissues from TCGA and GTEx databases and analyzed their relationship with survival of cervical cancer patients. In the end, the expression of key genes in cervical cancer tissues was verified via experiment method, we found KLF4 and ESR1 were downregulated in tumor tissues. Conclusion: This study indicates that KLF4 and ESR1 are downregulated by the upregulated miR21 and miRNA16 in cervical cancer, respectively, using bioinformatics analysis, and the lower expression of KLF4 and ESR1 is closely related to the poor prognosis. They might be of clinical significance for the diagnosis and prognosis of cervical cancer, and provide effective targets for the treatment of cervical cancer.

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Estrogen receptor promoter methylation predicts survival in low-grade ovarian carcinoma patients

Cited by 11 publications

References 24 publications

Galectins-1, -3, and -7 Are Prognostic Markers for Survival of Ovarian Cancer Patients

Galectins-1, -3, and -7 Are Prognostic Markers for Survival of Ovarian Cancer Patients

Big data-based identification of methylated genes associated with drug resistance and prognosis in ovarian cancer

<p>Identification of candidate biomarkers correlated with the diagnosis and prognosis of cervical cancer via integrated bioinformatics analysis</p>

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