Assessment of the Diagnostic Utility of Serum MicroRNA Classification in Patients With Diffuse Glioma

Makoto Ohno, Juntaro Matsuzaki, Junpei Kawauchi, Yoshiaki Aoki, Junichiro Miura, Satoko Takizawa, Ken Kato, Hiromi Sakamoto, Yuko Matsushita, Masamichi Takahashi, Yasuji Miyakita, Koichi Ichimura, Yoshitaka Narita, Takahiro Ochiya

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

IMPORTANCE A blood-based screening tool for detecting diffuse glioma is necessary to improve clinical outcomes. OBJECTIVES To establish models using serum microRNAs to distinguish patients with diffuse glioma from control individuals without cancer (the Glioma Index) and to differentiate glioblastoma (GBM), primary central nervous system lymphoma (PCNSL), and metastatic brain tumors (the 3-Tumor Index). DESIGN, SETTING, AND PARTICIPANTS This retrospective, case-control diagnostic study included 157 patients with diffuse glioma and 109 patients with central nervous system (CNS) diseases other than diffuse glioma diagnosed from August 1, 2008, through May 1, 2016, and 314 sex- and age-matched controls without cancer. Samples of patients with diffuse glioma and controls were randomly divided into training and validation set 1, and those of patients with CNS diseases other than diffuse glioma were allocated to an exploratory set. Samples of patients with GBM, PCNSL, and metastatic brain tumorswere randomly divided into training and validation set 2. Datawere analyzed from April 1, 2018, to March 31, 2019. MAIN OUTCOMES AND MEASURES The expression of 2565 microRNAs was assessed, and the diagnostic performance was evaluated by calculating the area under the receiver operating characteristics curve (AUC), sensitivity, specificity, and accuracy. RESULTS A total of 580 patients were included in the analysis (309 [53.3%] male; median age, 57 years [range, 10-87 years]). In training set 1, 100 patients with diffuse glioma (median age, 56 years [range, 14-87 years]; 55 male [55.0%]) were compared with 200 control patients (median age, 56 years [range, 14-87 years]; 105 male [52.5%]), and the Glioma Index was constructed using 3 microRNAs (miR-4763-3p, miR-1915-3p, and miR-3679-5p). In validation set 1, the AUC was 0.99 (95%CI, 0.99-1.00); sensitivity, 0.95 (95%CI, 0.89-1.00); and specificity, 0.97 (95%CI, 0.93-1.00). The Glioma Index classified 39 of 42 PCNSL samples (92.9%) and 25 of 28 metastatic brain tumor samples (89.3%) as positive and 2 of 2 spinal tumors (100%) as negative in the exploratory set. In training set 2, 68 patients with GBM, 34 with PCNSL, and 23 with metastatic brain tumor were compared, and the 3-Tumor Index was constructed using 48 microRNAs. The 3-Tumor Index had an accuracy of 0.80, positively detecting 16 of 17 GBM samples (94.1%), 4 of 5 metastatic brain tumor samples (80.0%), and 4 of 8 PCNSL samples (50.0%) in validation set 2. CONCLUSIONS AND RELEVANCE This study appears to have identified promising serum microRNA combinations for detecting diffuse glioma and for assessing histologic features of brain tumors.

Original languageEnglish
Article numbere1916953
JournalJAMA network open
Volume2
Issue number12
DOIs
Publication statusPublished - 2019 Dec 6
Externally publishedYes

ASJC Scopus subject areas

  • General Medicine

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