Strijker Marin, van der Sijde Fleur, Suker Mustafa, Boermeester Marja A, Bonsing Bert A, Bruno Marco J, Busch Olivier R, Doukas Michail, van Eijck Casper H, Gerritsen Arja, Groot Koerkamp Bas, Haj Mohammad Nadia, van Hilst Jony, de Hingh Ignace H, van Hooft Jeanin E, Luyer Misha D, Quintus Molenaar I, Verheij Joanne, Waasdorp Cynthia, Wilmink Johanna W, Besselink Marc G, van Laarhoven Hanneke W, Bijlsma Maarten F
Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands.
Department of Surgery, Erasmus MC, University Medical Center Rotterdam, the Netherlands.
HPB (Oxford). 2021 Dec;23(12):1886-1896. doi: 10.1016/j.hpb.2021.05.001. Epub 2021 May 19.
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 (316 pg/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 (>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).
High circulating ADAM12 levels, as a proxy for activated stroma, predict survival benefit from adjuvant chemotherapy in PDAC, requiring validation in future studies.
我们评估了基质标志物解整合素金属蛋白酶12（ADAM12）作为胰腺导管腺癌（PDAC）和壶腹周围癌总生存期（OS）的术前预后及治疗预测标志物。
材料来自前瞻性的全国性荷兰胰腺生物样本库（2015 - 2017年）。我们纳入了因PDAC/壶腹周围癌或非侵袭性胰腺导管内乳头状黏液性肿瘤（IPMN，对照组）而接受手术切除且有术前血清样本的患者。ADAM12水平使用预先定义的临界值（316 pg/mL）进行二分法划分。进行单变量和多变量Cox回归分析（向后选择）。
215例PDAC和壶腹周围腺癌患者的ADAM12水平中位数为161（四分位间距79 - 352）pg/mL。ADAM12水平高（>316 pg/mL）在胰腺和壶腹周围腺癌总体组中预测OS较差（P = 0.04），但调整后无此结果。在远端胆管癌（n = 33）中，单变量分析显示ADAM12水平高预测OS较差（P = 0.02），但在PDAC中无此结果（P = 0.63）。ADAM12水平高的PDAC患者（n = 135）从辅助治疗中获益（OS中位数27个月对14个月，P = 0.02），而水平低的患者未获益（21个月对21个月，P = 0.87）。
高循环ADAM12水平作为活化基质的指标，预测PDAC患者辅助化疗的生存获益，需要在未来研究中进行验证。
