Genome-wide long non-coding RNAs identified a panel of novel plasma biomarkers for gastric cancer diagnosis
- 320 Downloads
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.
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.
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.
Plasma lncRNA FAM49B-AS, GUSBP11 and CTDHUT have a strong potential to serve as noninvasive biomarkers for GC diagnosis.
KeywordsPlasma LncRNA Diagnosis Biomarker Gastric cancer
Long non-coding RNAs
Carbohydrate antigen 242
Carbohydrate antigen 724
Quantitative real-time PCR
Receiver operating characteristic
Area under the curve
CTD highly upregulated transcript
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).
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.
- 12.Shi T, Gao G, Cao Y. Long noncoding RNAs as novel biomarkers have a promising future in cancer diagnostics. Dis Markers. 2016;9085195:10.Google Scholar
- 22.Liu J, Wang J, Song Y, Ma B, Luo J, Ni Z, et al. A panel consisting of three novel circulating lncRNAs, is it a predictive tool for gastric cancer? J Cell Mol Med. 2018;26:13640.Google Scholar
- 26.Arita T, Ichikawa D, Konishi H, Komatsu S, Shiozaki A, Shoda K, et al. Circulating long non-coding RNAs in plasma of patients with gastric cancer. Anticancer Res. 2013;33:3185–93.Google Scholar