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). Serum-based measurements of stromal activation through ADAM12 associate with poor prognosis in colorectal cancer. BMC cancer, 22(1), p. 394. BioMed Central 10.1186/s12885-022-09436-0
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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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
?? 466EAF1B54364F4FADA2E68A076E7AAD ?? 04 Faculty of Medicine > Service Sector > Institute of Pathology 04 Faculty of Medicine > Service Sector > Institute of Pathology > Translational Research Unit |
UniBE Contributor: |
Zlobec, Inti |
Subjects: |
500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health |
ISSN: |
1471-2407 |
Publisher: |
BioMed Central |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
14 Apr 2022 10:04 |
Last Modified: |
05 Dec 2022 16:18 |
Publisher DOI: |
10.1186/s12885-022-09436-0 |
PubMed ID: |
35413826 |
Uncontrolled Keywords: |
ADAM12 Colorectal cancer Prognostic marker Stroma |
BORIS DOI: |
10.48350/169312 |
URI: |
https://boris.unibe.ch/id/eprint/169312 |
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