Pancreatic Cancer Biomarkers in Saliva

Objective: Early detection of pancreatic cancer carries the greatest hope to improve survival in this deadly cancer. Saliva offers great advantages for the non-invasive surveillance of human health, yet is a long neglected body fluid for the detection of disease. Based on our recent technological developments and findings on oral cancer mRNA markers in saliva, we investigated the salivary transcriptome for the detection of pancreatic cancer.

Methods: Saliva was collected from patients with clinically confirmed chronic pancreatitis, pancreatic cancer and healthy controls. A transcriptomic discovery study was performed using the Affymetrix All-Exon-Array, profiling 9 pancreatic cancers and 11 healthy control saliva samples. By a novel RT-PCR pre-amplification and real-time PCR, a large number of candidate markers were validated in the initial study cohort and then using a second, independent sample set (13 pancreatic cancers, 11 chronic pancreatitis and 33 healthy controls) (t-test and Wilcoxon rank test).

Results: Microarray profiling lead to the selection of 38 candidate exon/transcripts elevated in pancreatic cancer patients' saliva. We confirmed the >4 fold elevation of 22 transcripts in the original sample cohort. The elevation of 14 of these 22 candidates was validated in the independent cohort.

Conclusions: This is the first report validating salivary mRNA markers for the detection of a systemic disease, pancreatic cancer. These results augment the value of saliva as a diagnostic medium, particularly its utility for systemic diseases. We further aim to use the “salivary exon expression profiling” technology to stratify early and locally advanced pancreatic cancer patients including controls with chronic pancreatitis or benign cysts. Additional validation studies with large sample cohorts are necessary to translate this finding into clinical applications, but could lead to the inclusion of saliva for the early detection of pancreatic cancer.

Supported by PHS grant R01 DE015970.