ADAM12 is a circulating marker for stromal activation in pancreatic cancer and predicts response to chemotherapy. (November 2018)

• Record Type: Journal Article
• Authors: Veenstra, V.; Damhofer, H.; Waasdorp, C.; Rijssen, L.; Vijver, M.; Dijk, F.; Wilmink, H.; Besselink, M.; Busch, O.; Chang, D.; Bailey, P.; Biankin, A.; Kocher, H.; Medema, J.; Li, J.; Jiang, R.; Pierce, D.; Laarhoven, H.; Bijlsma, M.
• Is Part Of: Oncogenesis. Volume 7(2018:Nov.)
• Page Start: 1
• Page End: 11
• Publication Date: 2018-11
• Subjects: Oncogenes -- Periodicals; Cell Transformation, Neoplastic; Oncogenes; Periodicals; Periodicals; Fulltext; Internet Resources; Periodicals; 616.994042
• DOI: 10.1038/s41389-018-0096-9
• Languages: English
• ISSNs: 2157-9024

Abstract

Abstract Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma that harbors tumor-promoting properties. No good biomarkers exist to monitor the effect of stromal targeting therapies or to predict response. We set out to identify such non-invasive markers for PDAC stroma and predict response to therapy. Gene expression datasets, co-culture experiments, xenografts, and patient samples were analyzed. Serum samples were measured from a cohort of 58 resected patients, and 87 metastatic or locally advanced PDAC patients. Baseline and follow-up levels were assessed in 372 additional metastatic PDAC patients who received nab-paclitaxel with gemcitabine (n = 184) or gemcitabine monotherapy (n = 188) in the phase III MPACT trial. Increased levels of ADAM12 were found in PDAC patients compared to healthy controls (p < 0.0001, n = 157 andn = 38). High levels of ADAM12 significantly associated with poor outcome in resected PDAC (HR 2.07, p = 0.04). In the MPACT trial survival was significantly longer for patients who received nab-paclitaxel and had undetectable ADAM12 levels before treatment (OS 12.3 m vs 7.9 mp = 0.0046). Consistently undetectable or decreased ADAM12 levels during treatment significantly associated with longer survival as well (OS 14.4 m and 11.2 m, respectively vs 8.3, p = 0.0054). We conclude that ADAM12 is a blood-borne proxy for stromal activation, the levels of which have prognostic significance and correlate with treatment benefit.