Serum-based measurements of stromal activation through ADAM12 associate with poor prognosis in colorectal cancer
Sanne ten Hoorn,
Cynthia Waasdorp,
Martijn G. H. van Oijen,
Helene Damhofer,
Anne Trinh,
Lan Zhao,
Lisanne J. H. Smits,
Sanne Bootsma,
Gabi W. van Pelt,
Wilma E. Mesker,
Linda Mol,
Kaitlyn K. H. Goey,
Miriam Koopman,
Jan Paul Medema,
Jurriaan B. Tuynman,
Inti Zlobec,
Cornelis J. A. Punt,
Louis Vermeulen,
Maarten F. Bijlsma
Affiliations
Sanne ten Hoorn
Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Imaging and Biomarkers
Cynthia Waasdorp
Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Imaging and Biomarkers
Martijn G. H. van Oijen
Amsterdam UMC location University of Amsterdam, Department of Medical Oncology, Cancer Center Amsterdam
Helene Damhofer
Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Imaging and Biomarkers
Anne Trinh
Department of Medical Oncology, Dana-Farber Cancer Institute
Lan Zhao
Department of Electronic Engineering, City University of Hong Kong
Lisanne J. H. Smits
Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Surgery, Cancer Center Amsterdam
Sanne Bootsma
Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Imaging and Biomarkers
Gabi W. van Pelt
Department of Surgery, Leiden University Medical Center
Wilma E. Mesker
Department of Surgery, Leiden University Medical Center
Linda Mol
Department of Data Management, Netherlands Comprehensive Cancer Center (IKNL)
Kaitlyn K. H. Goey
Department of Medical Oncology, University Medical Center Utrecht, Utrecht University
Miriam Koopman
Department of Medical Oncology, University Medical Center Utrecht, Utrecht University
Jan Paul Medema
Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Imaging and Biomarkers
Jurriaan B. Tuynman
Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Surgery, Cancer Center Amsterdam
Inti Zlobec
Institute of Pathology, University of Bern
Cornelis J. A. Punt
Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht University
Louis Vermeulen
Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Imaging and Biomarkers
Maarten F. Bijlsma
Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Imaging and Biomarkers
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 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.
