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A support vector machine and a random forest classifier indicates a 15-miRNA set related to osteosarcoma recurrence

Authors He Y, Ma J, Wang A, Wang W, Luo S, Liu Y, Ye X

Received 5 August 2017

Accepted for publication 8 November 2017

Published 5 January 2018 Volume 2018:11 Pages 253—269

DOI https://doi.org/10.2147/OTT.S148394

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Dr William Cho


Yunfei He,1,2,* Jun Ma,1,* An Wang,1,3,* Weiheng Wang,1 Shengchang Luo,1 Yaoming Liu,2 Xiaojian Ye1

1Department of Orthopaedics, Changzheng Hospital Affiliated with Second Military Medical University, Shanghai, 2Department of Orthopaedics, Lanzhou General Hospital of Lanzhou Military Command Region, Lanzhou, 3Department of Orthopaedics, Shanghai Armed Police Force Hospital, Shanghai, People’s Republic of China

*These authors contributed equally to this work

Background: Osteosarcoma, which originates in the mesenchymal tissue, is the prevalent primary solid malignancy of the bone. It is of great importance to explore the mechanisms of metastasis and recurrence, which are two primary reasons accounting for the high death rate in osteosarcoma.
Data and methods: Three miRNA expression profiles related to osteosarcoma were downloaded from GEO DataSets. Differentially expressed miRNAs (DEmiRs) were screened using MetaDE.ES of the MetaDE package. A support vector machine (SVM) classifier was constructed using optimal miRNAs, and its prediction efficiency for recurrence was detected in independent datasets. Finally, a co-expression network was constructed based on the DEmiRs and their target genes.
Results: In total, 78 significantly DEmiRs were screened. The SVM classifier constructed by 15 miRNAs could accurately classify 58 samples in 65 samples (89.2%) in the GSE39040 database, which was validated in another two databases, GSE39052 (84.62%, 22/26) and GSE79181 (91.3%, 21/23). Cox regression showed that four miRNAs, including hsa-miR-10b, hsa-miR-1227, hsa-miR-146b-3p, and hsa-miR-873, significantly correlated with tumor recurrence time. There were 137, 147, 145, and 77 target genes of the above four miRNAs, respectively, which were assigned to 17 gene ontology functionally annotated terms and 14 Kyoto Encyclopedia of Genes and Genomes pathways. Among them, the “Osteoclast differentiation” pathway contained a total of seven target genes and was analyzed further.
Conclusion: The 15-miRNAs-based SVM classifier provides a potential useful tool to predict the recurrence of osteosarcoma. Our results suggest the possible mechanisms of osteosarcoma metastasis and recurrence and provide fresh DEmiRs as potential biomarkers or therapeutic targets for osteosarcoma.

Keywords:
osteosarcoma, microRNA, lncRNA, SVM classifier, co-expression network

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