Serum microRNA profile enables preoperative diagnosis of uterine leiomyosarcoma

Abstract

Uterine leiomyosarcoma (ULMS) is the major subtype of uterine sarcoma (US) and contributes to uterine cancer deaths. Although preoperative diagnosis of US remains challenging, frequent application of laparoscopic surgery for benign uterine leiomyomas (ULM) requires precise exclusion of US. MicroRNAs are stably present in the bloodstream, and the application of circulating miRNAs as disease biomarkers has been recognized. In the present study, we aimed to identify diagnostic biomarkers for distinguishing US from ULM by focusing on circulating miRNAs. All serum samples were collected preoperatively between 2009 and 2017, and all cases were histopathologically diagnosed. Whole miRNA profiles were obtained using a miRNA microarray. By analyzing expression levels of the miRNAs, candidate miRNAs were selected based on diagnostic performance in discriminating US from ULM, and a diagnostic model was then constructed. A total of 90 serum samples were analyzed, and clustering analyses revealed that the profiles of ULMS were distinct from those of controls. Based on leave-one-out cross-validation, seven miRNAs were selected as biomarker candidates. Based on model construction, the optimal model consisted of two miRNAs (miR-1246 and miR-191-5p), with an area under the receiver operating characteristic curve (AUC) for identifying ULMS of 0.97 (95% confidence interval [CI], 0.91-1.00). In contrast, serum lactate dehydrogenase had an AUC of only 0.64 (95% CI, 0.34-0.94). Seven serum miRNAs with high diagnostic performance for preoperative US screening were detected, and a promising diagnostic model for ULMS was generated. K E Y W O R D Scirculating microRNA, diagnostic biomarkers, liquid biopsy, uterine leiomyosarcoma, uterine sarcoma | 3719 YOKOI et al.

A Novel Tool to Predict Early Death in Uterine Sarcoma Patients: A Surveillance, Epidemiology, and End Results-Based Study

“…Compared with the patients in the low-risk group, the patients in the high-risk group showed significant mutation characteristics. Yokoi A et al (19) constructed an effective diagnostic model for uterine leiomyosarcoma using seven serum miRNA (Mir-4430, Mir-6511b-5p, Mir-191-5p, Mir-451A, Mir-4485-5p, Mir-4635, and Mir-1246) with high diagnostic performance for preoperative screening of uterine sarcoma, and proved that serum miRNA could be used as a preoperative biomarker. Unfortunately, since the SEER database itself does not contain a large number of molecular markers, our study did not construct a model containing molecular markers.…”

Recurrent broad ligament leiomyosarcoma with pancreatic and thigh metastasis: a case report

“…Considering neither non-invasive imaging nor pathological examinations can lead to accurate and specific diagnosis of LMS, researchers are eager to find a diagnostic and therapeutic method at molecular level. A study applicating circulating miRNAs as uterine LMS biomarkers found that combination of mir-1246 and mir-191-5p reached a diagnostic rate of 97% [15]. Xiangqian Guo et al [2] identified 3 LMS molecular subtypes associated with distinct clinical outcomes, making a good exploration of individualized and comprehensive therapy of LMS.…”

The Role of miRNA and Related Pathways in Pathophysiology of Uterine Fibroids—From Bench to Bedside

“…They have selected 2 of them and reported that the optimal model of miR-191-5p and miR-1246 presented an area under the receiver operating characteristic curve (AUC) for identifying LMS of 0.97 with 95% confidence interval of 0.91-1.00. At the same time, serum LDH had the AUC of only 0.64 and 95% confidence interval of 0.34-0.94 [129]. Earlier in 2017, de Almeida et al [130] also presented data on miRNAs expression in UFs in differential diagnosis.…”

“…In 2019 Yokoi et al [129] published data supporting the feasibility of serum circulating miRNAs as potential UFs biomarkers. The authors studied 7 different miRNAs-miR-191-5p, miR-451a, miR-1246, miR-4430, miR-4485-5p, miR-4635, miR-6511b-5p.…”