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Clin Chem. 2018 Oct;64(10):1513-1521. doi: 10.1373/clinchem.2018.290569. Epub 2018 Aug 10.

Discovery and Validation of Salivary Extracellular RNA Biomarkers for Noninvasive Detection of Gastric Cancer.

Author information

1
Institute of Diagnostic in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China.
2
School of Dentistry, University of California, Los Angeles, CA.
3
Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
4
Department of Medicine Statistics Core, David Geffen School of Medicine, University of California, Los Angeles, CA.
5
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA.
6
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
7
Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
8
School of Dentistry, University of California, Los Angeles, CA; dtww@ucla.edu thadyk@ucla.edu sungkimm@skku.edu.
9
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; dtww@ucla.edu thadyk@ucla.edu sungkimm@skku.edu.

Abstract

BACKGROUND:

Biomarkers are needed for noninvasive early detection of gastric cancer (GC). We investigated salivary extracellular RNA (exRNA) biomarkers as potential clinical evaluation tools for GC.

METHODS:

Unstimulated whole saliva samples were prospectively collected from 294 individuals (163 GC and 131 non-GC patients) who underwent endoscopic evaluation at the Samsung Medical Center in Korea. Salivary transcriptomes of 63 GC and 31 non-GC patients were profiled, and mRNA biomarker candidates were verified with reverse transcription quantitative real-time PCR (RT-qPCR). In parallel, microRNA (miRNA) biomarkers were profiled and verified with saliva samples from 10 GC and 10 non-GC patients. Candidate biomarkers were validated with RT-qPCR in an independent cohort of 100/100 saliva samples from GC and non-GC patients. Validated individual markers were configured into a best performance panel.

RESULTS:

We identified 30 mRNA and 15 miRNA candidates whose expression pattern associated with the presence of GC. Among them, 12 mRNA and 6 miRNA candidates were verified with the discovery cohort by RT-qPCR and further validated with the independent cohort (n = 200). The configured biomarker panel consisted of 3 mRNAs (SPINK7, PPL, and SEMA4B) and 2 miRNAs (MIR140-5p and MIR301a), which were all significantly down-regulated in the GC group, and yielded an area under the ROC curve (AUC) of 0.81 (95% CI, 0.72-0.89). When combined with demographic factors, the AUC of the biomarker panel reached 0.87 (95% CI, 0.80-0.93).

CONCLUSIONS:

We have discovered and validated a panel of salivary exRNA biomarkers with credible clinical performance for the detection of GC. Our study demonstrates the potential utility of salivary exRNA biomarkers in screening and risk assessment for GC.

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