Identification of serum microRNAs in genome-wide serum microRNA expression profiles as novel noninvasive biomarkers for malignant peripheral nerve sheath tumor diagnosis.

Recent studies found that serum microRNAs (miRNAs) could serve as stable and noninvasive biomarkers for disease diagnosis. We used genome-wide serum miRNA expression analysis to investigate the role of serum miRNAs in distinguishing malignant peripheral nerve sheath tumor (MPNST) patients with and without neurofibromatosis type 1 (NF1) from NF1 patients. A total of 100 patients with NF1, 93 sporadic MPNST patients, and 71 NF1 MPNST patients were enrolled in this two-stage, case-control study. Solexa sequencing was used to screen for miRNAs that expressed differentially in three pooled serum samples from 10 NF1 patients, 10 sporadic MPNST patients, and 10 NF1 MPNST patients. The detected serum miRNAs then were validated in 90 patients with NF1, 83 patients with sporadic MPNST, and 61 NF1 MPNST patients by individual quantitative reverse transcriptase polymerase chain reaction assays. Eight serum miRNAs altered more than fivefold by Solexa sequencing between MPNST patients (with and without NF1) and NF1 patients. MiR-801 and miR-214 increased both in sporadic MPNST patients and NF1 MPNST patients when compared with NF1 patients. The sensitivity and the specificity of sporadic MPNST detection by the two-miRNA signature were 0.747 and 0.856, respectively. MiR-24 was only significantly up-regulated in NF1 MPNST patients. The combination of the three miRNAs (MiR-801, miR-214, and miR-24) could distinguish NF1 MPNST patients from NF1 patients with a sensitivity of 0.820 and a specificity of 0.844. The serum-based miRNA expression profiles could serve as novel noninvasive biomarkers in sporadic MPNST and NF1 MPNST detection.