MMP7 is an Independent Predictor of Pathologic Response Utilizing FNA Specimens of Pancreatic Ductal Adenocarcinoma

Objective: The use of biomarkers for patient selection and predicting therapy response is integral to precision medicine. Our aim was to evaluate the utility of treatment-naïve fine needle aspirate (FNA) specimens in predicting pathologic response (PR) to NAT.
Design: RNA sequencing of frozen FNA specimens were performed on a discovery cohort of 23 specimens obtained before NAT in order to identify biomarkers differently expressed in these specimens that may be associated with NAT. A further 80 FNA specimens from treatment naïve patients were immunohistochemically stained to validate protein expression and correlation with PR.
Results: In the discovery cohort, RNA sequencing showed that lower MMP-7 expression was associated with favorable PR (score 0 and 1)(P=0.016). In the validation cohort, patients with negative MMP-7 expression were significantly more likely to have a favorable PR (odds ratio=21.25, P=0.001). ROC curves for prediction of favorable PR from multivariable regression modelling showed that MMP-7 expression increased area under the curve from 0.726 to 0.906 (P<0.001) even after stratifying by resectability status. The positive predictive value and negative predictive value of MMP-7 protein expression on FNA specimens in predicting unfavorable PR were 88.2% and 73.9%, respectively.
Conclusion: Assessment of the expression of MMP-7 on FNA specimens at the time of diagnosis may help in identifying patients who will benefit most from NAT.