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Utility of Serum miR-125b as a Diagnostic and Prognostic Indicator and Its Alliance with a Panel of Tumor Suppressor Genes in Epithelial Ovarian Cancer.

Zuberi M, Khan I, Mir R, Gandhi G, Ray PC, Saxena A - PLoS ONE (2016)

Bottom Line: Expression of miR-125b was found to be significantly upregulated (p<0.0001) in comparison with healthy controls.The expression level of miR-125b was found to be significantly associated with FIGO stage, lymph node and distant metastasis.Our results indicate that DNA hypermethylation may be involved in the inactivation of miR-125b and miR-125b may function as a potential independent biomarker for clinical outcome in EOC.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Maulana Azad Medical College and Associated Hospitals, New Delhi, India.

ABSTRACT
MicroRNAs (miRNAs) have been found to be dysregulated in epithelial ovarian cancer (EOC) and may function as either tumor suppressor genes (TSGs) or as oncogenes. Hypermethylation of miRNA silences the tumour suppressive function of a miRNA or hypermethylation of a TSG regulating that miRNA (or vice versa) leads to its loss of function. The present study aims to evaluate the impact of aberrant microRNA-125b (miR-125b) expression on various clinicopathological features in epithelial ovarian cancer and its association with anomalous methylation of several TSGs. We enrolled 70 newly diagnosed cases of epithelial ovarian cancer, recorded their clinical history and 70 healthy female volunteers. Serum miR-125b levels were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and the methylation status of various TSGs was investigated by methylation specific PCR. ROC curves were constructed to estimate the diagnostic and prognostic usefulness of miR-125b. The Kaplan-Meier method was applied to compare survival curves. Expression of miR-125b was found to be significantly upregulated (p<0.0001) in comparison with healthy controls. The expression level of miR-125b was found to be significantly associated with FIGO stage, lymph node and distant metastasis. ROC curve for diagnostic potential yielded significant AUC with an equitable sensitivity and specificity. ROC curves for prognosis yielded significant AUCs for histological grade, distal metastasis, lymph node status and survival. The expression of miR-125b also correlated significantly with the hypermethylation of TSGs. Our results indicate that DNA hypermethylation may be involved in the inactivation of miR-125b and miR-125b may function as a potential independent biomarker for clinical outcome in EOC.

No MeSH data available.


Related in: MedlinePlus

Association of miR-125b expression with the promoter hypermethylation of a panel of tumour suppressor genes.(A)DAPK1 (B) p16 (C) RASSF1A (D) PTEN (E) BRCA1 (F) p14. Positive and negative depicts the presence or absence of promoter hypermethylation of the specified tumour suppressor gene respectively.
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pone.0153902.g005: Association of miR-125b expression with the promoter hypermethylation of a panel of tumour suppressor genes.(A)DAPK1 (B) p16 (C) RASSF1A (D) PTEN (E) BRCA1 (F) p14. Positive and negative depicts the presence or absence of promoter hypermethylation of the specified tumour suppressor gene respectively.

Mentions: The relative expression of miR-125b was assessed in relation to the promoter hypermethylation of well known tumour suppressor genes—DAPK1, p16, RASSF1A, PTEN, BRCA1 and p14. Out of these, RASSF1A and PTEN genes showed a statistically significant correlation between the aberrant hypermethylation of their promoter and the relative expression of miR-125b in epithelial ovarian cancer patients. Patients with RASSF1A promoter hypermethylation demonstrated downregulation of miR-125b expression (p = 0.005) (Fig 5). Similarly, patients with PTEN promoter hypermethylation showed downregulation of miR-125b expression (p = 0.01). No other tumour suppressor gene exhibited a statistically significant association with miR-125b expression.


Utility of Serum miR-125b as a Diagnostic and Prognostic Indicator and Its Alliance with a Panel of Tumor Suppressor Genes in Epithelial Ovarian Cancer.

Zuberi M, Khan I, Mir R, Gandhi G, Ray PC, Saxena A - PLoS ONE (2016)

Association of miR-125b expression with the promoter hypermethylation of a panel of tumour suppressor genes.(A)DAPK1 (B) p16 (C) RASSF1A (D) PTEN (E) BRCA1 (F) p14. Positive and negative depicts the presence or absence of promoter hypermethylation of the specified tumour suppressor gene respectively.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4836713&req=5

pone.0153902.g005: Association of miR-125b expression with the promoter hypermethylation of a panel of tumour suppressor genes.(A)DAPK1 (B) p16 (C) RASSF1A (D) PTEN (E) BRCA1 (F) p14. Positive and negative depicts the presence or absence of promoter hypermethylation of the specified tumour suppressor gene respectively.
Mentions: The relative expression of miR-125b was assessed in relation to the promoter hypermethylation of well known tumour suppressor genes—DAPK1, p16, RASSF1A, PTEN, BRCA1 and p14. Out of these, RASSF1A and PTEN genes showed a statistically significant correlation between the aberrant hypermethylation of their promoter and the relative expression of miR-125b in epithelial ovarian cancer patients. Patients with RASSF1A promoter hypermethylation demonstrated downregulation of miR-125b expression (p = 0.005) (Fig 5). Similarly, patients with PTEN promoter hypermethylation showed downregulation of miR-125b expression (p = 0.01). No other tumour suppressor gene exhibited a statistically significant association with miR-125b expression.

Bottom Line: Expression of miR-125b was found to be significantly upregulated (p<0.0001) in comparison with healthy controls.The expression level of miR-125b was found to be significantly associated with FIGO stage, lymph node and distant metastasis.Our results indicate that DNA hypermethylation may be involved in the inactivation of miR-125b and miR-125b may function as a potential independent biomarker for clinical outcome in EOC.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Maulana Azad Medical College and Associated Hospitals, New Delhi, India.

ABSTRACT
MicroRNAs (miRNAs) have been found to be dysregulated in epithelial ovarian cancer (EOC) and may function as either tumor suppressor genes (TSGs) or as oncogenes. Hypermethylation of miRNA silences the tumour suppressive function of a miRNA or hypermethylation of a TSG regulating that miRNA (or vice versa) leads to its loss of function. The present study aims to evaluate the impact of aberrant microRNA-125b (miR-125b) expression on various clinicopathological features in epithelial ovarian cancer and its association with anomalous methylation of several TSGs. We enrolled 70 newly diagnosed cases of epithelial ovarian cancer, recorded their clinical history and 70 healthy female volunteers. Serum miR-125b levels were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and the methylation status of various TSGs was investigated by methylation specific PCR. ROC curves were constructed to estimate the diagnostic and prognostic usefulness of miR-125b. The Kaplan-Meier method was applied to compare survival curves. Expression of miR-125b was found to be significantly upregulated (p<0.0001) in comparison with healthy controls. The expression level of miR-125b was found to be significantly associated with FIGO stage, lymph node and distant metastasis. ROC curve for diagnostic potential yielded significant AUC with an equitable sensitivity and specificity. ROC curves for prognosis yielded significant AUCs for histological grade, distal metastasis, lymph node status and survival. The expression of miR-125b also correlated significantly with the hypermethylation of TSGs. Our results indicate that DNA hypermethylation may be involved in the inactivation of miR-125b and miR-125b may function as a potential independent biomarker for clinical outcome in EOC.

No MeSH data available.


Related in: MedlinePlus