Oncotarget

Research Papers:

Exosomes containing differential expression of microRNA and mRNA in osteosarcoma that can predict response to chemotherapy

Ji-Feng Xu, Ya-Ping Wang, Shui-Jun Zhang, Yu Chen, Hai-Feng Gu, Xiao-Fan Dou, Bing Xia, Qing Bi and Shun-Wu Fan _

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Oncotarget. 2017; 8:75968-75978. https://doi.org/10.18632/oncotarget.18373

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Abstract

Ji-Feng Xu2,3, Ya-Ping Wang1, Shui-Jun Zhang2, Yu Chen2, Hai-Feng Gu2, Xiao-Fan Dou2, Bing Xia2, Qing Bi2 and Shun-Wu Fan3

1Department of Cardiology, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang 310009, P.R. China

2Department of Orthopedics, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China

3Department of Orthopedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China

Correspondence to:

Shun-Wu Fan, email: [email protected]

Keywords: osteosarcoma (OS), chemotherapy sensitivity, exosome, microRNA, poor chemotherapeutic response

Received: January 12, 2017     Accepted: April 15, 2017     Published: June 06, 2017

ABSTRACT

A major challenge in osteosarcoma (OS) is the selection of the most effective chemotherapeutic agents for individual patients, while the administration of ineffective chemotherapy increases mortality and decreases quality of life in patients. This emphasizes the need to evaluate every patient's probability of responding to each chemotherapeutic agent. We developed a profiling strategy for serum exosomal microRNAs and mRNAs in OS patients with differential chemotherapeutic responses. Twelve miRNAs were up regulated and 18 miRNAs were under regulated significantly in OS patient with poor chemotherapeutic response when compared with those in good chemotherapeutic response (p<0.05). In addition, miR-124, miR133a, miR-199a-3p, and miR-385 were validated and significantly reduced in poorly responded patients with an independent OS cohort. While miR-135b, miR-148a, miR-27a, and miR-9 were significantly over expressed in serum exosomes. Bioinformatic analysis by DIANA-mirPath demonstrated that Proteoglycans in cancer, Hippo signaling pathway, Pathways in cancer, Transcriptional misregulation in cancer, PI3K-Akt signaling pathway, Ras signaling pathway, Ubiquitin mediated proteolysis, Choline metabolism in cancer were the most prominent pathways enriched in quantiles with the miRNA patterns related to poor chemotherapeutic response. Messenger RNAs(mRNAs) includingAnnexin2, Smad2, Methylthioadenosine phosphorylase (MTAP), Cdc42-interacting protein 4 (CIP4), Pigment Epithelium-Derived Factor (PEDF), WW domain-containing oxidoreductase (WWOX), Cell division cycle 5-like (Cdc5L), P27 were differentially expressed in exosomes in OS patients with different chemotherapeutic response. These data demonstrated that exosomal RNA molecules are reliable biomarkers in classifying osteosarcoma with different chemotherapy sensitivity.


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