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Cancer Chemotherapy and Pharmacology

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01-08-2019 | Colorectal Cancer | Original Article

A panel of serum exosomal microRNAs as predictive markers for chemoresistance in advanced colorectal cancer

Authors: Guoying Jin, Yuhang Liu, Jia Zhang, Zehua Bian, Surui Yao, Bojian Fei, Leyuan Zhou, Yuan Yin, Zhaohui Huang

Published in: Cancer Chemotherapy and Pharmacology | Issue 2/2019

Abstract

Background

Chemoresistance is a common problem for cancer treatment worldwide. Circulating exosomal microRNAs (miRNAs) have been considered as promising biomarkers of cancers. However, few studies have assessed the relationship between serum/plasma exosomal microRNAs and chemoresistance in colorectal cancer (CRC).

Methods

Based on previous microarray analysis, we selected 30 miRNAs which are aberrantly expressed during CRC progression and then detected their expression levels in three pairs of oxaliplatin/5-fluorouracil-resistant CRC cell lines and the corresponding secreted exosomes. Six candidate exosomal miRNAs were identified for further evaluating potential value in predicting chemotherapeutic effect in advanced CRC patients. Finally, the molecular mechanisms of these miRNAs in drug resistance were explored by bioinformatics preliminarily.

Results

We observed that the expression of 14 miRNAs was significantly higher in three drug-resistant CRC cells comparing with their parental cells. Among these miRNAs, miR-21-5p, miR-1246, miR-1229-5p, miR-135b, miR-425 and miR-96-5p are also up-regulated in exosomes from culture media of resistant cells. Clinical sample analysis confirmed that the expression levels of miR-21-5p, miR-1246, miR-1229-5p and miR-96-5p in serum exosomes were significantly higher in chemoresistant patients in contrast with chemosensitive controls. ROC curve showed that the combination of the four miRNAs had an area of under the curve (AUC) of 0.804 (P < 0.05). In addition, GO analysis and KEGG pathway analysis revealed that these miRNAs were enriched in PI3K-Akt signaling pathway, FoxO signaling pathway and autophagy pathway.

Conclusions

Our study demonstrates that a panel of serum exosomal miRNAs containing miR-21-5p, miR-1246, miR-1229-5p and miR-96-5p could significantly distinguish the chemotherapy-resistant group from advanced colorectal cancer patients. Targeting these miRNAs may promote chemosensitivity to oxaliplatin and 5-fluorouracil, and might be promising strategy for CRC treatment.

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Title: A panel of serum exosomal microRNAs as predictive markers for chemoresistance in advanced colorectal cancer
Authors: Guoying Jin
Yuhang Liu
Jia Zhang
Zehua Bian
Surui Yao
Bojian Fei
Leyuan Zhou
Yuan Yin
Zhaohui Huang
Publication date: 01-08-2019
Publisher: Springer Berlin Heidelberg
Keywords: Colorectal Cancer
Colorectal Cancer
Cytostatic Therapy
Published in: Cancer Chemotherapy and Pharmacology / Issue 2/2019
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-019-03867-6

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