Plasma-derived exosomal miR-15a-5p as a promising diagnostic biomarker for early detection of endometrial carcinoma

Abstract

Endometrial cancer (EC) is a major cause of death among gynecologic malignancies. To improve early detection of EC in patients, we carried out a large plasma-derived exosomal microRNA (miRNA) studies for diagnostic biomarker discovery in EC. Small RNA sequencing was performed to identify candidate exosomal miRNAs as diagnostic biomarkers in 56 plasma samples from healthy subjects and EC patients. These miRNA candidates were further validated in 202 independent plasma samples by droplet digital PCR (ddPCR), 32 pairs of endometrial tumors and adjacent normal tissues by quantitative real-time PCR (qRT-PCR), and matched plasma samples of 12 patients before and after surgery by ddPCR. miR-15a-5p, miR-106b-5p, and miR107 were significantly upregulated in exomes isolated from plasma samples of EC patients compared with healthy subjects. Particularly, miR-15a-5p alone yielded an AUC value of 0.813 to distinguish EC patients with stage I from healthy subjects. The integration of miR-15a-5p and serum tumor markers (CEA and CA125) achieved a higher AUC value of 0.899. There was also a close connection between miR-15a-5p and clinical manifestations in EC patients. Its exosomal expression was not only associated with the depth of muscular infiltration and aggressiveness of EC, but also correlated with levels of reproductive hormones such as TTE and DHEAS. Collectively, plasma-derived exosomal miR-15a-5p is a promising and effective diagnostic biomarker for the early detection of endometrial cancer.

miRNAs in the Expression Regulation of Dopamine-Related Genes and Proteins in Endometrial Cancer

“…Kong et al noticed that high expression of miR-15a-5p led to the promotion of cell proliferation and invasion in glioblastoma [ 25 ], which was also confirmed in ovarian cancer [ 26 ]. Interestingly, the studies conducted so far indicate that the level of miR-15a-5p was reduced both in the serum of patients [ 27 ] and in endometrial cancer cells and tissues [ 28 ]. Our results, therefore, may suggest that the interaction of this miRNA with DRD5 may play a role in the progression of endometrial cancer by regulating its proliferation.…”

Exosomes as a new frontier of cancer liquid biopsy

“…For instance, mutant EGFRvIII mRNA was detected in serum exosomes of glioblastoma patients [ 39 ]. Zhou et al reported that the expression level of exosomal miR-15a-5p was 7-19 times higher in endometrial cancer than that in other cancer types [ 40 ]. Additionally, high expression of exosomal miR-1247-3p was positively associated with lung metastasis from liver cancer, which indicated a poor outcome [ 41 ].…”

New Trends in the Detection of Gynecological Precancerous Lesions and Early-Stage Cancers

“…Interestingly, several studies have identified miRNAs in extracellular vesicles from different body fluids, e.g., urine [ 124 ], peritoneal lavage [ 125 ], and blood serum [ 126 ]. Recently, a large plasma-derived exosomal miRNA study identified miR-15a-5p as a valuable diagnostic biomarker for the early detection of EC [ 127 ]. Another study identified four miRNAs associated with EC (oncogenic miRNAs miR-135b and miR-205, as well as tumor suppressor miRNAs miR-30a-3p and miR-21) [ 123 ].…”

“…Therefore, a two-step strategy, using both CA-125 and TVS, has been developed. Several studies have used a two-phase strategy to detect early-stage ovarian tumors and have confirmed its good specificity and positive predictive value in a population of women at a moderate risk of ovarian cancer [ 3 , 127 , 128 ].…”