TITLE: “Salivary exRNA for Gastric Cancer Detection”
ABSTRACT: Biomarkers are needed for non-invasive early detection of gastric cancer (GC). We investigated whether salivary extracellular RNA (exRNA) biomarkers can be used as an efficient and economical clinical evaluation tool for GC. Unstimulated whole saliva samples were prospectively collected from 294 subjects (163 GC and 131 non-GC controls) who underwent endoscopic evaluation at the Samsung Medical Center in Korea. The salivary transcriptomes of 63 GC and 31 non-GC controls were profiled, and mRNA biomarker candidates were verified with RT-qPCR. In parallel, microRNA biomarkers were profiled and verified with saliva samples from 10 GC and 10 controls. 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. We identified 30 mRNA and 15 miRNA candidates whose expression pattern associated with the presence of gastric cancer. 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 (miR-140-5p and miR-301a), which were all significantly down-regulated in GC group, yielded an AUC of 0.81 (95%CI, 0.72-0.89). When combined with demographic factors, the performance of the panel reached an AUC of 0.87 (95%CI, 0.80-0.93). We have discovered and validated a panel of salivary exRNA biomarkers with credible clinical performance for the detection of GC. Our study demonstrates the credential of salivary exRNA biomarker as a potential screening and risk-assessing tool for GC.