Stool DNA testing for the detection of pancreatic cancer
Kisiel JB et al. – This study demonstrates that stool assay of a methylated gene marker can detect PanC. Among candidate methylated markers discriminant in tissue, BMP3 alone performed well in stool. Combining methylated BMP3 and mutant KRAS increased stool detection over either marker alone.Methods
- Nine target genes were assayed by real-time methylation-specific polymerase chain reaction (MSP) in bisulfite-treated DNA from microdissected frozen specimens of 24 PanC cases and 30 normal colon controls.
- Archived stools from 58 PanC cases and 65 controls matched on sex, age, and smoking were analyzed.
- Target genes from fecal supernatants were enriched by hybrid capture, bisulfite-treated, and assayed by MSP.
- KRAS mutations were assayed using the QuARTS technique.
- Areas under the receiver operating characteristics curves (AUCs) for tissue BMP3, NDRG4, EYA4, UCHL1, MDFI, Vimentin, CNTNAP2, SFRP2, and TFPI2 were 0.90, 0.79, 0.78, 0.78, 0.77, 0.77, 0.69, 0.67, and 0.66, respectively.
- The top 4 markers and mutant KRAS were evaluated in stool.
- BMP3 was the most discriminant methylation marker in stool.
- At 90% specificity, methylated BMP3 alone detected 51% of PanCs, mutant KRAS detected 50%, and combination detected 67%.
- AUCs for methylated BMP3, mutant KRAS, and combination in stool were 0.73, 0.75, and 0.85, respectively.