title: Profiling analysis of circulating microRNA expression in cervical cancer.
abstract: MicroRNA (miRNA) expression is altered in cancer cells and is associated with the development and progression of various types of cancer. Accordingly, miRNAs may serve as diagnostic or prognostic biomarkers in cancer patients. In this study, we attempted to analyze circulating exosomal miRNA in patients with cervical cancer. Total RNA was extracted from the serum of healthy subjects, subjects with cervical intraepithelial neoplasia (CIN) and patients with cervical cancer. We first investigated miRNA expression profiles in 6 serum samples from healthy subjects and patients with cervical cancer using the miRCURY LNA microRNA array. miRNAs with significant differences in expression were validated in a larger sample set by quantitative reverse transcription-polymerase chain reaction, using TaqMan gene expression assays. The results of the miRCURY LNA microRNA array indicated that 6 of 1,223 miRNAs found in serum samples from cervical cancer patients and normal controls exhibited a >3.0-fold change in expression level in subjects with cervical cancer, with a P-value of <0.01. In a validation set (n=131) that investigated the expression of 4 of the 6 miRNAs (miR-483-5p, miR-1246, miR-1275 and miR-1290), miR-1290 was found to have significantly higher expression levels in cervical cancer samples (n=45) compared with control samples (n=31). We also found that the median levels of these miRNAs were significantly higher in subjects with cervical cancer (n=45) compared with those in subjects with CIN (n=55). Circulating miRNAs were not correlated with clinicopathological parameters. However, receiver operating characteristic curve analysis suggested that these serum miRNAs may be useful diagnostic markers in cervical cancer. The expression of circulating miR-1290 was significantly higher in the blood of cervical cancer patients compared with that in controls and may thus serve as a useful biomarker in cervical cancer diagnosis. However, larger studies are required to fully elucidate the role of circulating exosomal miRNAs in cervical cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo 160-0023, Japan.
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Nagamitsu
authors.affiliation: Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo 160-0023, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Nishi
authors.affiliation: Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo 160-0023, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo 160-0023, Japan.
authors.forename: Yotaro
authors.initials: Y
authors.lastname: Takaesu
authors.affiliation: Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo 160-0023, Japan.
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Terauchi
authors.affiliation: Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo 160-0023, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Isaka
keywords: biomarker; cervical cancer; miR-1290; microRNA