Abstract
Purpose: Circulating microRNAs (miRNAs) prove to be promising diagnostic biomarkers for various cancers, including endometrial cancer (EC). The present study aims to identify serum microRNAs that can serve as potential biomarkers for EC diagnosis.Patients and methods: A total of 92 EC and 102 normal control (NC) serum samples were analyzed using quantitative real-time polymerase chain reaction (qRT-PCR) in this four-phase experiment. The logistic regression method was used to construct a diagnostic model based on the differentially expressed miRNAs in serum. The receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value. To further validate the diagnostic capacity of the identified signature, the 6-miRNA marker was compared with previously reported biomarkers and verified in three public datasets. In addition, the expression characteristics of the identified miRNAs were further explored in tissue and serum exosomes samples.Results: Six miRNAs (miR-143-3p, miR-195-5p, miR-20b-5p, miR-204-5p, miR-423-3p, and miR-484) were significantly overexpressed in the serum of EC compared with NCs. Areas under the ROC of the 6-miRNA signatures were 0.748, 0.833, and 0.967 for the training, testing, and the external validation phases, respectively. The identified signature has a very stable diagnostic performance in the large cohorts of three public datasets. Compared with previously identified miRNA biomarkers, the 6-miRNA signature in the present study has superior performance in diagnosing EC. Moreover, the expression of miR-143-3p and miR-195-5p in tissues and the expression of miR-20b-5p in serum exosomes were consistent with those in serum.Conclusions: We established a 6-miRNA signature in serum and they could function as potential non-invasive biomarker for EC diagnosis.
Highlights
Endometrial cancer (EC) is one of the most frequent female malignancies and the fourth leading cause of cancer-related deaths among women worldwide [1,2]
There was no significant difference in the distribution of age between EC patients and normal control (NC) during the four stages (P>0.05)
The expression profile of 174 miRNAs was measured by the Exiqon miRCURY-Ready-to-Use polymerase chain reaction (PCR)-Human-panel-I+II-V1.M in 2 peripheral serum pools from 20 EC patients and 1 pooled sample from 10 female NCs
Summary
Endometrial cancer (EC) is one of the most frequent female malignancies and the fourth leading cause of cancer-related deaths among women worldwide [1,2]. 74000 women were expected to die of EC each year [3]. In China, approximately 50000 new cases of EC are added each year, and the number of deaths is 18000. Most guidelines recommend either transvaginal ultrasonography or endometrial biopsy as the initial test, but none of them are completely satisfactory. Diagnostic curettage is a widely used diagnostic method in EC patients. Diagnostic curettage has several inherent defects, such as invasive nature. Diagnostic curettage needs to be operated by experienced gynecologists and has a risk of missed diagnosis.
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