Diagnostic Significance in Estimating Tumor Burden Using Extracellular Salivary Biomarkers in Gastric Cancer Patients.

We investigated the possibility of predicting tumor burden with salivary extracellular RNA (exRNA) biomarkers in gastric cancer patients. Saliva samples were prospectively collected from 50 gastric cancer patients who underwent gastrectomy with curative intent. Approximately 5 mL of saliva was collected before surgery and on the 5th to 7th days after surgery. The expression of three mRNAs (SPINK7, PPL, and SEMA4B) and two miRNAs (miR140-5p and miR301a) that were previously validated was determined by reverse transcription quantitative real-time PCR. There were significant differences in the pre-operative expression of PPL ( = 0.025), SEMA4B ( = 0.012), and miR140-5p ( = 0.036) between pathologic stage I/II and III/IV groups. The area under the curve (AUC) of each respective multivariable model in predicting stage III/IV, which was adjusted for age and sex, was 75.4% (PPL), 82.5% (SEMA4B), and 75.5% (miR140-5p). In the multivariable model, including all three biomarkers, the AUC was 89.2%. On the other hand, none of the conventional tumor markers (CEA, CA19-9, and CA72-4) could predict tumor burden before surgery. The AUC of the multivariable model, including CEA, CA19-9, and CA72-4, was 67.2%, 66.2%, and 67.4%, respectively. When all three tumor markers were included in the multivariable model, the AUC was 70.5%. Noninvasively detected salivary biomarkers have been shown to have higher diagnostic accuracy than conventional tumor markers detected by invasive blood tests for estimating pre-operative tumor burden. This study demonstrates the potential utility of these biomarkers in pre-operative risk assessment and monitoring surgical treatment response to gastric cancer.