Abstract
BACKGROUND: 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.
METHODS: 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 (316 pg/mL). Univariable and multivariable Cox regression analyses (backward selection) were performed.
RESULTS: Median ADAM12 levels were 161 (IQR 79-352) pg/mL in 215 PDAC and periampullary adenocarcinomas. High ADAM12 levels (>316 pg/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).
CONCLUSION: High circulating ADAM12 levels, as a proxy for activated stroma, predict survival benefit from adjuvant chemotherapy in PDAC, requiring validation in future studies.
Original language | English |
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Pages (from-to) | 1886-1896 |
Number of pages | 11 |
Journal | HPB: The official journal of the International Hepato Pancreato Biliary Association |
Volume | 23 |
Issue number | 12 |
Early online date | 2021 |
DOIs | |
Publication status | Published - Dec 2021 |
Keywords
- ADAM12 Protein/blood
- Adenocarcinoma/drug therapy
- Carcinoma, Pancreatic Ductal/drug therapy
- Humans
- Pancreas
- Pancreatic Neoplasms/drug therapy
- Prognosis
- Prospective Studies
- Retrospective Studies