Serum-based measurements of stromal activation through ADAM12 associate with poor prognosis in colorectal cancer
ten Hoorn, Sanne; Waasdorp, Cynthia; van Oijen, Martijn G.H.; Damhofer, Helene; Trinh, Anne; Zhao, Lan; Smits, Lisanne J.H.; Bootsma, Sanne; van Pelt, Gabi W.; Mesker, Wilma E.; Mol, Linda; Goey, Kaitlyn K.H.; Koopman, Miriam; Medema, Jan Paul; Tuynman, Jurriaan B.; Zlobec, Inti; Punt, Cornelis J.A.; Vermeulen, Louis; Bijlsma, Maarten F.
(2022) BMC Cancer, volume 22, issue 1
(Article)
Abstract
Background: Recently it has been recognized that stromal markers could be used as a clinically relevant biomarker for therapy response and prognosis. Here, we report on a serum marker for stromal activation, A Disintegrin and Metalloprotease 12 (ADAM12) in colorectal cancer (CRC). Methods: Using gene expression databases we investigated ADAM12
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expression in CRC and delineated the source of ADAM12 expression. The clinical value of ADAM12 was retrospectively assessed in the CAIRO2 trial in metastatic CRC with 235 patients (31% of total cohort), and an independent rectal cancer cohort (n = 20). Results: ADAM12 is expressed by activated CRC associated fibroblasts. In the CAIRO2 trial cohort, ADAM12 serum levels were prognostic (ADAM12 low versus ADAM12 high; median OS 25.3 vs. 17.1 months, HR 1.48 [95% CI 1.11–1.96], P = 0.007). The prognostic potential was specifically high for metastatic rectal cancer (HR 1.78 [95% CI 1.06–3.00], P = 0.030) and mesenchymal subtype tumors (HR 2.12 [95% CI 1.25–3.60], P = 0.004). ADAM12 also showed potential for predicting recurrence in an exploratory analysis of non-metastatic rectal cancers. Conclusions: Here we describe a non-invasive marker for activated stroma in CRC which associates with poor outcome, especially for primary cancers located in the rectum.
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Keywords: ADAM12, Colorectal cancer, Prognostic marker, Stroma, ADAM12 Protein/genetics, Cancer-Associated Fibroblasts/metabolism, Prognosis, Colorectal Neoplasms/pathology, Humans, Biomarkers, Tumor/genetics, Rectal Neoplasms, Biomarkers, Retrospective Studies, Colonic Neoplasms, Genetics, Oncology, Cancer Research, Journal Article
ISSN: 1471-2407
Publisher: BioMed Central
Note: Funding Information: This work is supported by the Dutch Cancer Society (KWF, 10529, 10651 and 2012–5584) to L.V., M.F.B., J.P.M and C.P. The European Research Council (ERG-StG 638193), ZonMw (Vidi 016.156.308), and Innovatiefonds Zorgverzekeraars (B17–140) to L.V. L.V. is a New York Stem Cell Foundation – Robertson Investigator. Funding Information: MFB has received research funding from Celgene and LEAD pharma, and has acted as a consultant to Servier. LV received speaker and consultancy fees from Genentech, Bayer, Servier, Boehringer-Ingelheim, MSD and Pierre Fabre. LV received unrestricted grants from Novartis, Servier, Roche and Roche Diagnostics. LV declares ongoing collaborations with Firalis, LeadPharma and Genentech. CP reports an advisory role for Nordic Pharma. AT is a scientific advisor for GenieUs Genomics. MK reports having an advisory role for Nordic Farma, Merck-Serono, Pierre Fabre, Servier, and institutional scientific grants from Bayer, Bristol Myers Squibb, Merck, Roche, Servier. No disclosures were reported by the other authors. None of the funders had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2022, The Author(s).
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