Preoperative serum ADAM12 levels as a stromal marker for overall survival and benefit of adjuvant therapy in patients with resected pancreatic and periampullary cancer

Marin Strijker*, Fleur van der Sijde, for the Dutch Pancreatic Cancer Group, Mustafa Suker, Marja A. Boermeester, Bert A. Bonsing, Marco J. Bruno, Olivier R. Busch, Michail Doukas, Casper H. van Eijck, Arja Gerritsen, Bas Groot Koerkamp, Nadia Haj Mohammad, Jony van Hilst, Ignace H. de Hingh, Jeanin E. van Hooft, Misha D. Luyer, I. Quintus Molenaar, Joanne Verheij, Cynthia WaadorpJohanna W. Wilmink, Marc G. Besselink, Hanneke W. van Laarhoven, Maarten F. Bijlsma

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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 languageEnglish
Pages (from-to)1886-1896
Number of pages11
JournalHPB
Volume23
Issue number12
DOIs
Publication statusPublished - 1 Dec 2021

Bibliographical note

Funding Information:
HWL has acted as a consultant for Celgene, Eli Lilly and Company, Nordic Pharma Group, Merck, Novartis, Servier and Philips, has received research grants from Amgen, Bayer Schering Pharma AG, Celgene, Eli Lilly and Company, GlaxoSmithKline Pharmaceuticals, Merck, Nordic Pharma Group, Philips, Roche Pharmaceuticals and Servier.

Funding Information:
MDL has received grants from Medtronic, Galvani and Nutricia.

Funding Information:
IdH has received grants from Roche Pharmaceutical, QPS/RanD and Medtronic.

Funding Information:
MFB has received research funding from Celgene and acted as a consultant for Servier. MFB is inventor on a patent application describing the use of serum ADAM12 levels in gastrointestinal cancers.

Funding Information:
This work was supported by the Dutch Cancer Society [grant number UVA2013-5842 ] and the AMC foundation . This work was carried out in the context of Parelsnoer clinical biobanks at Health-RI.

Funding Information:
JEH has acted as a consultant for Boston Scientific, Cook Medical, Medtronics and has received research grants from Cook Medical and Abbott.

Funding Information:
This work was supported by the Dutch Cancer Society [grant number UVA2013-5842] and the AMC foundation.

Funding Information:
MJB has received research funding from Boston Scientific, Cook Medical, Pentax Medical, Mylan and 3 M, and acted as a consultant Boston Scientific, Cook Medical, Pentax Medical, Mylan and 3 M.

Publisher Copyright:
© 2021 The Authors

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