Abstract
We evaluated the stroma marker A Disintegrin And Metalloprotease 12 (ADAM12) as a preoperative prognostic and treatment-predictive marker for overall survival (OS) in pancreatic ductal adenocarcinoma (PDAC) and periampullary cancers. Materials were derived from the prospective nationwide Dutch Pancreas Biobank (2015-2017). We included patients who underwent resection because of PDAC/periampullary cancer or non-invasive IPMN (control group) and had a preoperative serum sample available. ADAM12 levels were dichotomized using a pre-defined cut-off (316pg/mL). Univariable and multivariable Cox regression analyses (backward selection) were performed. Median ADAM12 levels were 161 (IQR 79-352) pg/mL in 215 PDAC and periampullary adenocarcinomas. High ADAM12 levels (>316pg/mL) predicted poor OS in the total group of pancreatic and periampullary adenocarcinomas (P=0.04), but not after adjustment. In distal cholangiocarcinoma (n=33), high ADAM12 levels predicted poor OS in univariable analysis (P=0.02), but not in PDAC (P=0.63). PDAC patients (n=135) with high ADAM12 levels benefited from adjuvant treatment (median OS 27 vs 14 months, P=0.02), whereas those with low levels did not (21 vs 21 months, P=0.87). High circulating ADAM12 levels, as a proxy for activated stroma, predict survival benefit from adjuvant chemotherapy in PDAC, requiring validation in future studies.
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