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.
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.
Department of Biochemistry, Maulana Azad Medical College and Associated Hospitals, New Delhi, India.
Mariyam
M
Zuberi
Department of Surgery, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Imran
I
Khan
Prince Fahd Bin Sultan Research Chair, Faculty of Applied Medical Sciences, University of Tabuk, Saudi Arabia, Tabuk-71491.
Rashid
R
Mir
Department of Gynaecology and Obstetrics, Lok Nayak Hospital, New Delhi, India.
Gauri
G
Gandhi
Department of Biochemistry, Maulana Azad Medical College and Associated Hospitals, New Delhi, India.
Prakash Chandra
PC
Ray
Department of Biochemistry, Maulana Azad Medical College and Associated Hospitals, New Delhi, India.
Alpana
A
Saxena
D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics*; D000077216:Carcinoma, Ovarian Epithelial; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D012372:ROC Curve; D015854:Up-Regulation / Q000235:genetics
D014408:Biomarkers, Tumor; C531888:MIRN125 microRNA, human; D035683:MicroRNAs