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Genome-wide long non-coding RNAs identified a panel of novel plasma biomarkers for gastric cancer diagnosis

  • Rui Zheng
  • Jiayuan Liang
  • Jiafei Lu
  • Shuwei Li
  • Gang Zhang
  • Xiaowei Wang
  • Mengting Liu
  • Weizhi Wang
  • Haiyan Chu
  • Guoquan Tao
  • Qinghong Zhao
  • Meilin Wang
  • Mulong Du
  • Fulin Qiang
  • Zhengdong Zhang
Original Article
  • 103 Downloads

Abstract

Background

Although long non-coding RNAs (lncRNAs) are regarded as useful plasma-based biomarkers for cancer detection, the potential diagnostic value of lncRNAs in gastric cancer (GC) remains unclear.

Methods

To screen promising lncRNAs biomarkers for GC, we performed genome-wide lncRNA microarray assay between five GC cases plasma and matched healthy controls plasma. The expression of candidate plasma-related lncRNAs were validated in two-phase validation of 446 subjects. The receiver operating characteristic curve was constructed for evaluating diagnostic accuracy. We also determined the origin and stability of plasma lncRNAs, and investigated biological effects of candidate lncRNAs on cellular phenotypes.

Results

A total of 3878 lncRNAs were expressed differentially in GC plasma, among which the top 10 up-regulated lncRNAs were selected for further validation. A two-stage validation revealed that plasma levels of three lncRNAs (FAM49B-AS, GUSBP11, and CTDHUT) were significantly higher in GC plasma as compared with healthy controls (P < 0.05), and the combined area under curve of these lncRNAs was 0.818 (95% CI 0.772–0.864). Moreover, these lncRNAs were stable and detectable in human plasma, and also enriched in extracellular fluid. The expression levels of all three lncRNAs dropped significantly on day 10 after radical surgery compared with preoperative levels (P < 0.05). Also, lncRNA FAM49B-AS significantly promoted GC cell viability and invasion.

Conclusions

Plasma lncRNA FAM49B-AS, GUSBP11 and CTDHUT have a strong potential to serve as noninvasive biomarkers for GC diagnosis.

Keywords

Plasma LncRNA Diagnosis Biomarker Gastric cancer 

Abbreviations

lncRNAs

Long non-coding RNAs

GC

Gastric cancer

CI

Confidence interval

SPG

Serum pepsinogen

CA242

Carbohydrate antigen 242

CA724

Carbohydrate antigen 724

CEA

Carcinoembryonic antigen

ncRNAs

Non-coding RNAs

qRT-PCR

Quantitative real-time PCR

PI

Propidium iodide

Ct

Cycle threshold

ROC

Receiver operating characteristic

AUC

Area under the curve

CTDHUT

CTD highly upregulated transcript

Notes

Acknowledgements

This study was supported by National Natural Science Foundation of China (81473049, 81773538 and 81773539), Jiangsu Provincial Science and Technology Innovation Team, Jiangsu Provincial Postdoctoral Science Foundation funded project (1501081C), China Postdoctoral Science Foundation funded project (2015M580449), Collaborative Innovation Center For Cancer Personalized Medicine, and the Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine).

Author contributions

ZZ, QF, DM and WM designed the research. WW, ZQ, TG and ZG recruited samples. ZR, LJ, LJ, LS, WX, LM and CH contributed reagents/materials/analysis tools. ZR, LJ and LJ wrote the manuscript. All authors reviewed the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Human rights statement and informed consent

The research was approved by the Ethics Committee of Nanjing Medical University. Informed consent was obtained from all subjects before they were included in this study.

Supplementary material

10120_2018_915_MOESM1_ESM.docx (6.9 mb)
Supplementary material 1 (DOCX 7050 KB)

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Copyright information

© The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2019

Authors and Affiliations

  • Rui Zheng
    • 1
    • 2
  • Jiayuan Liang
    • 1
    • 2
  • Jiafei Lu
    • 1
    • 2
  • Shuwei Li
    • 1
    • 2
  • Gang Zhang
    • 1
    • 2
    • 3
  • Xiaowei Wang
    • 1
    • 2
  • Mengting Liu
    • 1
    • 2
  • Weizhi Wang
    • 4
  • Haiyan Chu
    • 1
    • 2
  • Guoquan Tao
    • 5
  • Qinghong Zhao
    • 6
  • Meilin Wang
    • 1
    • 2
    • 7
  • Mulong Du
    • 1
    • 8
  • Fulin Qiang
    • 9
  • Zhengdong Zhang
    • 1
    • 2
    • 7
  1. 1.Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjingChina
  2. 2.Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public HealthNanjing Medical UniversityNanjingChina
  3. 3.Department of NeurologyThe Affiliated Children’s Hospital of Nanjing Medical UniversityNanjingChina
  4. 4.Department of General SurgeryThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  5. 5.Department of General SurgeryThe Affiliated Huaian No.1 People’s Hospital of Nanjing Medical UniversityHuai’anChina
  6. 6.Department of General SurgeryThe Second Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  7. 7.Department of Environmental Genomics, Center for Global Health, School of Public HealthNanjing Medical UniversityNanjingChina
  8. 8.Department of Biostatistics, Center for Global Health, School of Public HealthNanjing Medical UniversityNanjingChina
  9. 9.Department of Core LaboratoryNantong Tumor HospitalNantongChina

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