Excessive collagen turnover products are released during colorectal cancer progression and elevated in serum from metastatic colorectal cancer patients

During cancer progression, the homeostasis of the extracellular matrix becomes imbalanced with an excessive collagen remodeling by matrix metalloproteinases. As a consequence, small protein fragments of degraded collagens are released into the circulation. We have investigated the potential of protein fragments of collagen type I, III and IV as novel biomarkers for colorectal cancer. Specific fragments of degraded type I, III and IV collagen (C1M, C3M, C4M) and type III collagen formation (Pro-C3) were assessed in serum from colorectal cancer patients, subjects with adenomas and matched healthy controls using well-characterized and validated ELISAs. Serum levels of the biomarkers were significantly elevated in colorectal cancer patients compared to subjects with adenomas (C1M, Pro-C3, C3M) and controls (C1M, Pro-C3). When patients were stratified according to their tumour stage, all four biomarkers were able to differentiate stage IV metastatic patients from all other stages. Combination of all markers with age and gender in a logistic regression model discriminated between metastatic and non-metastatic patients with an AUROC of 0.80. The data suggest that the levels of these collagen remodeling biomarkers may be a measure of tumour activity and invasiveness and may provide new clinical tools for monitoring of patients with advanced stage colorectal cancer

The ECCO-Darwin Data-Assimilative Global Ocean Biogeochemistry Model: Estimates of Seasonal to Multidecadal Surface Ocean \u3cem\u3ep\u3c/em\u3eCO\u3csub\u3e2\u3c/sub\u3e and Air-Sea CO\u3csub\u3e2\u3c/sub\u3e Flux

Quantifying variability in the ocean carbon sink remains problematic due to sparse observations and spatiotemporal variability in surface ocean pCO2. To address this challenge, we have updated and improved ECCO-Darwin, a global ocean biogeochemistry model that assimilates both physical and biogeochemical observations. The model consists of an adjoint-based ocean circulation estimate from the Estimating the Circulation and Climate of the Ocean (ECCO) consortium and an ecosystem model developed by the Massachusetts Institute of Technology Darwin Project. In addition to the data-constrained ECCO physics, a Green\u27s function approach is used to optimize the biogeochemistry by adjusting initial conditions and six biogeochemical parameters. Over seasonal to multidecadal timescales (1995–2017), ECCO-Darwin exhibits broad-scale consistency with observed surface ocean pCO2 and air-sea CO2 flux reconstructions in most biomes, particularly in the subtropical and equatorial regions. The largest differences between CO2 uptake occur in subpolar seasonally stratified biomes, where ECCO-Darwin results in stronger winter uptake. Compared to the Global Carbon Project OBMs, ECCO-Darwin has a time-mean global ocean CO2 sink (2.47 ± 0.50 Pg C year−1) and interannual variability that are more consistent with interpolation-based products. Compared to interpolation-based methods, ECCO-Darwin is less sensitive to sparse and irregularly sampled observations. Thus, ECCO-Darwin provides a basis for identifying and predicting the consequences of natural and anthropogenic perturbations to the ocean carbon cycle, as well as the climate-related sensitivity of marine ecosystems. Our study further highlights the importance of physically consistent, property-conserving reconstructions, as are provided by ECCO, for ocean biogeochemistry studies

The ECCO‐Darwin Data‐Assimilative Global Ocean Biogeochemistry Model: Estimates of Seasonal to Multidecadal Surface Ocean pCO₂ and Air‐Sea CO₂ Flux

Quantifying variability in the ocean carbon sink remains problematic due to sparse observations and spatiotemporal variability in surface ocean pCO₂. To address this challenge, we have updated and improved ECCO‐Darwin, a global ocean biogeochemistry model that assimilates both physical and biogeochemical observations. The model consists of an adjoint‐based ocean circulation estimate from the Estimating the Circulation and Climate of the Ocean (ECCO) consortium and an ecosystem model developed by the Massachusetts Institute of Technology Darwin Project. In addition to the data‐constrained ECCO physics, a Green's function approach is used to optimize the biogeochemistry by adjusting initial conditions and six biogeochemical parameters. Over seasonal to multidecadal timescales (1995–2017), ECCO‐Darwin exhibits broad‐scale consistency with observed surface ocean pCO₂ and air‐sea CO₂ flux reconstructions in most biomes, particularly in the subtropical and equatorial regions. The largest differences between CO₂ uptake occur in subpolar seasonally stratified biomes, where ECCO‐Darwin results in stronger winter uptake. Compared to the Global Carbon Project OBMs, ECCO‐Darwin has a time‐mean global ocean CO₂ sink (2.47 ± 0.50 Pg C year⁻¹) and interannual variability that are more consistent with interpolation‐based products. Compared to interpolation‐based methods, ECCO‐Darwin is less sensitive to sparse and irregularly sampled observations. Thus, ECCO‐Darwin provides a basis for identifying and predicting the consequences of natural and anthropogenic perturbations to the ocean carbon cycle, as well as the climate‐related sensitivity of marine ecosystems. Our study further highlights the importance of physically consistent, property‐conserving reconstructions, as are provided by ECCO, for ocean biogeochemistry studies