Abstract
microRNAs (miRNAs) play important roles in regulation of gene expression during cervical carcinogenesis. We investigated expression profiles of miRNAs in cervical cancer and its precursor lesions by utilizing cervical mucus. Cervical mucus was collected from 230 patients with a normal cervix, cervical intraepithelial neoplasia (CIN), squamous cell carcinoma (SCC), or adenocarcinoma (AD). The levels of miRNA in the mucus were quantified by miRNA array and real-time reverse-transcriptase polymerase chain reaction (RT-PCR). The performance for detecting diseases was statistically analysed. The expression of miRNAs was further validated in the surgical tissues of enrolled patients. Four miRNAs (miR-126-3p, -20b-5p, -451a, and -144-3p) were significantly up-regulated in SCC and AD compared with normal, and their expression levels correlated with disease severity and high-risk human papillomavirus infection. Receiver operating characteristic curve analyses revealed that the area under the curve values for miR-126-3p, -20b-5p, -451a, and -144-3p were 0.89, 0.90, 0.94, and 0.93, respectively, for SCC plus AD compared with normal, showing high accuracy of cancer detection. Real-time RT-PCR analyses confirmed the expression of these four miRNAs in frozen tissues from cervical cancer. miR-126-3p, -20b-5p, -451a, and -144-3p in cervical mucus are promising biomarkers for cervical cancer and high-grade CINs.
Highlights
Cervical cancer is the fourth most common cancer in women, with an estimated 528,000 new cases and 265,000 deaths worldwide in 20121–3, and approximately 90% of cervical cancer deaths occur in developing countries
To identify miRNAs that are up-regulated in cervical cancer compared to normal cervix, we performed miRNA microarray analysis using total RNA extracted from cervical mucus
Among 2588 miRNAs tested, 76 miRNAs were selected as potential biomarker candidates according to the following criteria: the absolute value of the signal intensity was more than 20, and the relative ratio of the squamous cell carcinoma (SCC) vs. normal or adenocarcinoma (AD) vs. normal was more than four
Summary
Cervical cancer is the fourth most common cancer in women, with an estimated 528,000 new cases and 265,000 deaths worldwide in 20121–3, and approximately 90% of cervical cancer deaths occur in developing countries. Persistent infection with a high-risk human papillomavirus (HPV), is a necessary cause of cervical cancer development. HPV DNA tests have been introduced into the screening system because these tests exhibit high sensitivity compared to cytology. Their specificity is inferior because most HPV infections are transient and do not clinically manifest as cervical lesions. The results of these studies were not always consistent, and were inconclusive as to the roles of miRNAs in supporting or suppressing cervical carcinogenesis. This may be due to differences in the source of materials or methods used for analysis
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