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Exosomal miR-1246 in serum as a potential biomarker for early diagnosis of gastric cancer

  • Yuntao  Shi
  • Zhonghong  Wang
  • Xiaojuan  Zhu
  • Ling  Chen
  • Yilan  Ma
  • Jiayan  Wang
  • Xiaozhong  YangEmail author
  • Zheng  LiuEmail author
Original Article
  • 27 Downloads

Abstract

Background

Gastric cancer (GC) patients are usually diagnosed in advanced stages which results in high mortality. This study aimed to identify novel circulating miRNAs as biomarkers for the early detection of GC.

Methods

Candidate miRNA was identified after integrated analysis of two Gene Expression Omnibus (GEO) datasets and clinical serum samples. Exosomes extracted were verified using transmission electron microscopy (TEM) and western blot. The expressions of miRNAs were tested through qRT-PCR. Receiver operating characteristic curve (ROC) analysis was used to explore the diagnostic utility of miRNAs. RNA pull-down assay was used to find RNA binding proteins (RBPs) which transport candidate miRNA into exosomes. Bioinformatics analysis of candidate miRNA was conducted using DAVID and Cytoscape.

Results

After integrated analysis of two GEO datasets, six circulating miRNAs were found to be consistently upregulated in GC patients. Then, qRT-PCR demonstrated that serum miR-1246 was the one with the largest fold change. Studies in vitro revealed that elevated serum miR-1246 was tumor-derived by being packaged into exosomes with the help of ELAVL1. Thereafter, we discovered that exosomal miR-1246 expressions in serum could differentiate GC patients with TNM stage I from healthy controls (HCs) and patients with benign diseases (BDs) with area under the curve (AUC) of 0.843 and 0.811, respectively. Bioinformatics analysis revealed miR-1246, as a tumor suppressor in GC, could regulate several signaling pathways.

Conclusion

Circulating exosomal miR-1246 was a potential biomarker for the early diagnosis of GC.

Keywords

Exosomes miR-1246 Gastric cancer Diagnosis Biomarker 

Notes

Compliance with ethical standards

Conflict of interest

The authors report no conflicts of interest in this work.

Ethical approval

This study was approved by the Research and Ethical Committee of The Second Affiliated Hospital of Nanjing Medical University.

Informed consent

Written informed consent was obtained from all participants

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Copyright information

© Japan Society of Clinical Oncology 2019

Authors and Affiliations

  • Yuntao  Shi
    • 1
    • 2
  • Zhonghong  Wang
    • 3
  • Xiaojuan  Zhu
    • 1
  • Ling  Chen
    • 1
  • Yilan  Ma
    • 1
  • Jiayan  Wang
    • 1
  • Xiaozhong  Yang
    • 2
    Email author
  • Zheng  Liu
    • 1
    Email author
  1. 1.Medical Center for Digestive DiseasesThe Second Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  2. 2.Department of GastroenterologyThe Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical UniversityHuaianChina
  3. 3.Department of GastroenterologyHuaian People’s Hospital of Hongze DistrictHuaianChina

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