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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

Serum expression of miR-125b.(A) Dot plot showing the relative expression of miR-125b in patients and controls (B) ROC curve for miR-125b exhibiting its diagnostic potential in epithelial ovarian cancer.
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pone.0153902.g001: Serum expression of miR-125b.(A) Dot plot showing the relative expression of miR-125b in patients and controls (B) ROC curve for miR-125b exhibiting its diagnostic potential in epithelial ovarian cancer.

Mentions: Real time relative quantification analysis showed more than 5 fold increase in serum miR-125b expression among epithelial ovarian cancer patients than healthy controls (Table 3). ROC curve analyses were performed to evaluate the predictive power of miR-125b for malignant ovarian cancer and illustrated in Fig 1. Relative expression of the serum miR-125b could discriminate patients with malignant ovarian cancer from healthy controls, with a power AUC of 0.728 (95% CI = 0.64–0.81) at a sensitivity of 62.3% and specificity of 77.1% from a cut-off score of 3.76.


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)

Serum expression of miR-125b.(A) Dot plot showing the relative expression of miR-125b in patients and controls (B) ROC curve for miR-125b exhibiting its diagnostic potential in epithelial ovarian cancer.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0153902.g001: Serum expression of miR-125b.(A) Dot plot showing the relative expression of miR-125b in patients and controls (B) ROC curve for miR-125b exhibiting its diagnostic potential in epithelial ovarian cancer.
Mentions: Real time relative quantification analysis showed more than 5 fold increase in serum miR-125b expression among epithelial ovarian cancer patients than healthy controls (Table 3). ROC curve analyses were performed to evaluate the predictive power of miR-125b for malignant ovarian cancer and illustrated in Fig 1. Relative expression of the serum miR-125b could discriminate patients with malignant ovarian cancer from healthy controls, with a power AUC of 0.728 (95% CI = 0.64–0.81) at a sensitivity of 62.3% and specificity of 77.1% from a cut-off score of 3.76.

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