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

  • Guoying Jin
  • Yuhang Liu
  • Jia Zhang
  • Zehua Bian
  • Surui Yao
  • Bojian Fei
  • Leyuan Zhou
  • Yuan YinEmail author
  • Zhaohui HuangEmail author
Original Article
  • 65 Downloads

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.

Keywords

Colorectal cancer Chemoresistance Exosome MicroRNAs 

Notes

Funding

This study was partially supported by grants from the National Natural Science Foundation of China (81672328 and 81772636), Fundamental Research Funds for the Central Universities (NOJUSRP51619B and JUSRP51710A), Medical Key Professionals Program of Jiangsu Province (AF052141), Medical Youth Professionals Program of Jiangsu Province (QNRC2016162), Medical Innovation Team Program of Wuxi (CXTP003), National First-class Discipline Program of Food Science and Technology (JUFSTR20180101), Project of the Wuxi Health and Family Planning Commission (Z201806).

Compliance with ethical standards

Conflict of interest

No potential conflicts of interest were disclosed.

Supplementary material

280_2019_3867_MOESM1_ESM.tif (24.7 mb)
Supplementary material 1 (TIFF 25310 kb)
280_2019_3867_MOESM2_ESM.docx (45 kb)
Supplementary material 2 (DOCX 45 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Guoying Jin
    • 1
    • 2
  • Yuhang Liu
    • 1
    • 2
  • Jia Zhang
    • 1
    • 2
  • Zehua Bian
    • 1
    • 2
  • Surui Yao
    • 1
    • 2
  • Bojian Fei
    • 3
  • Leyuan Zhou
    • 4
  • Yuan Yin
    • 1
    • 2
    Email author
  • Zhaohui Huang
    • 1
    • 2
    Email author
  1. 1.Wuxi Cancer InstituteAffiliated Hospital of Jiangnan UniversityWuxiChina
  2. 2.Cancer Epigenetics Program, Wuxi School of MedicineJiangnan UniversityWuxiChina
  3. 3.Department of Surgical OncologyAffiliated Hospital of Jiangnan UniversityWuxiChina
  4. 4.Department of Radiation OncologyThe Affiliated Hospital of Jiangnan UniversityWuxiChina

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