Serum microRNA profile enables preoperative diagnosis of uterine leiomyosarcoma

Akira Yokoi, Juntaro Matsuzaki, Yusuke Yamamoto, Keisei Tate, Yutaka Yoneoka, Hanako Shimizu, Takashi Uehara, Mitsuya Ishikawa, Satoko Takizawa, Yoshiaki Aoki, Ken Kato, Tomoyasu Kato, Takahiro Ochiya

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3718-3726
Number of pages9
JournalCancer science
Volume110
Issue number12
DOIs
Publication statusPublished - 2019 Dec 1
Externally publishedYes

Keywords

  • circulating microRNA
  • diagnostic biomarkers
  • liquid biopsy
  • uterine leiomyosarcoma
  • uterine sarcoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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