title: Expression and prognostic value of microRNAs in lower-grade glioma depends on IDH1/2 status.
abstract: Histological and genomic characteristics are widely used in glioma management and research. This study investigated their relationship to the expression and prognostic value of microRNAs (miRNAs) in lower-grade glioma (LGG). A total of 447 LGG samples with available clinical and genomic information from The Cancer Genome Atlas database were reviewed. Samples with isocitrate dehydrogenase (IDH) 1/2 mutations (n = 366) were randomly divided into training and validation sets to establish and confirm a four-miRNA-based risk classifier. We found that IDH1/2 mutation status had greater impact than histological and other genomic features on miRNA expression patterns; 361/487 (74%) of miRNAs were differentially expressed according to IDH1/2 mutation status. Importantly, there were no miRNAs with the same prognostic significance among groups with different IDH1/2 mutation status. For IDH1/2-mut LGG, a four-miRNA risk classifier (miR-10b, miR-130b, miR-1304, and miR-302b) was established that could independently distinguish cases as high or low risk of poor prognosis in both training and validation sets. The risk classifier outperformed individual miRNAs and traditional prognostic factors in terms of sensitivity and specificity. Bioinformatic analyses indicated that high-risk samples were more mitotically active than low-risk samples. Taken together, IDH1/2 mutation status had a significant influence on miRNA expression and prognostication in LGG. The four-miRNA-based risk classifier can be used for risk stratification of IDH1/2-mut LGG.
authors.affiliation: Department of Neurosurgery, The First Hospital of China Medical University, Nanjing Street 155, Heping District, Shenyang, 110001, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Xiufang
authors.initials: X
authors.lastname: Ren
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
authors.forename: Chuanbao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The First Hospital of China Medical University, Nanjing Street 155, Heping District, Shenyang, 110001, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Neurosurgery, The First Hospital of China Medical University, Nanjing Street 155, Heping District, Shenyang, 110001, China. wuanhua@yahoo.com.
authors.forename: Anhua
authors.initials: A
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D019295:Computational Biology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D063990:Gene Ontology; D005910:Glioma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011379:Prognosis; D012044:Regression Analysis; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D035683:MicroRNAs; D007521:Isocitrate Dehydrogenase
keywords: Genomic aberration; IDH1/2 mutation; Lower-grade glioma; MicroRNA profile; Prognostic classifier