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Abstract
A desmoplastic colorectal cancer stroma, characterized by excess turnover of the cancer-associated fibroblast derived collagens type III and VI, can lead to reduced drug-uptake and poor treatment response. We investigated the association between biomarkers of collagen type III and VI and overall survival (OS) in patients with metastatic colorectal cancer (mCRC). Serum samples were collected from 252 patients with mCRC prior to treatment with bevacizumab and chemotherapy. Serum concentrations of biomarkers reflecting formation of collagen type III (PRO-C3) and VI (PRO-C6) and degradation of collagen type VI (C6M and C6Mα3) were determined by ELISA. The biomarkers were evaluated for associations with OS, individually, combined, and after adjusting for carcinoembryonic antigen (CEA), lactate dehydrogenase (LDH) and performance status (PS). High baseline levels (> median) of each collagen biomarker were significantly associated with shorter OS (PRO-C3: HR = 2.0, 95%CI = 1.54–2.63; PRO-C6: HR = 1.6, 95%CI = 1.24–2.11; C6M: HR = 1.4, 95%CI = 1.05–1.78; C6Mα3: HR = 1.6, 95%CI = 1.16–2.07). PRO-C3 and PRO-C6 remained significant after adjustment for CEA, LDH and PS. Weak correlations were seen between the collagen biomarkers (r = 0.03–0.59) and combining all improved prognostic capacity (HR = 3.6, 95%CI = 2.30–5.76). Collagen biomarkers were predictive of shorter OS in patients with mCRC. This supports that collagen- and CAF biology is important in CRC.
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Details
1 University of Copenhagen (UCPH), Biotech Research and Innovation Centre (BRIC), Copenhagen, Denmark (GRID:grid.5254.6) (ISNI:0000 0001 0674 042X); Nordic Bioscience, Biomarkers and Research, Herlev, Denmark (GRID:grid.436559.8) (ISNI:0000 0004 0410 881X)
2 Nordic Bioscience, Biomarkers and Research, Herlev, Denmark (GRID:grid.436559.8) (ISNI:0000 0004 0410 881X)
3 Copenhagen University Hospital, Department of Oncology, Herlev and Gentofte Hospital, Copenhagen, Denmark (GRID:grid.4973.9) (ISNI:0000 0004 0646 7373)
4 Karolinska University Hospital Huddinge, Department of Clinical Science, Intervention and Technology, Stockholm, Sweden (GRID:grid.24381.3c) (ISNI:0000 0000 9241 5705)
5 Copenhagen University Hospital, Department of Oncology, Herlev and Gentofte Hospital, Copenhagen, Denmark (GRID:grid.4973.9) (ISNI:0000 0004 0646 7373); Copenhagen University Hospital, Department of Medicine, Herlev and Gentofte Hospital, Copenhagen, Denmark (GRID:grid.4973.9) (ISNI:0000 0004 0646 7373); University of Copenhagen, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Copenhagen, Denmark (GRID:grid.5254.6) (ISNI:0000 0001 0674 042X)
6 University of Copenhagen (UCPH), Biotech Research and Innovation Centre (BRIC), Copenhagen, Denmark (GRID:grid.5254.6) (ISNI:0000 0001 0674 042X)