Single-EV analysis (sEVA) of mutated proteins allows detection of stage 1 pancreatic cancer

Tumor cell-derived extracellular vesicles (EVs) are being explored as circulating biomarkers, but it is unclear whether bulk measurements will allow early cancer detection. We hypothesized that a single-EV analysis (sEVA) technique could potentially improve diagnostic accuracy. Using pancreatic cancer (PDAC), we analyzed the composition of putative cancer markers in 11 model lines. In parental PDAC cells positive for KRAS(mut) and/or P53(mut) proteins, only similar to 40% of EVs were also positive. In a blinded study involving 16 patients with surgically proven stage 1 PDAC, KRAS(mut) and P5S(mut) protein was detectable at much lower levels, generally in <0.1% of vesicles. These vesicles were detectable by the new sEVA approach in 15 of the 16 patients. Using a modeling approach, we estimate that the current PDAC detection limit is at similar to 0.1-cm(3) tumor volume, below clinical imaging capabilities. These findings establish the potential for sEVA for early cancer detection.

Automated summary

This study shows that tumor cell-derived extracellular vesicles (EVs) have potential as circulating biomarkers for early cancer detection. Single-EV analysis (sEVA) technique improves diagnostic accuracy for pancreatic cancer (PDAC), even when the levels of KRAS(mut) and P53(mut) proteins are low.