Body Fatness, Adipose Tissue Compartments, and Biomarkers of Inflammation and Angiogenesis in Colorectal Cancer: The ColoCare Study

Himbert, Caroline; Ose, Jennifer; Nattenmüller, Johanna; Warby, Christy A.; Holowatyj, Andreana N.; Böhm, Jürgen; Lin, Tengda; Haffa, Mariam; Gigic, Biljana; Hardikar, Sheetal; Scherer, Dominique; Zielske, Lin; Schrotz‐King, Petra; Kölsch, Torsten; Siegel, Erin M.; Shibata, David; Ulrich, Alexis; Schneider, Martin; Hursting, Stephen D.; Kauczor, Hans Ulrich; Ulrich, Cornelia M.

doi:10.1158/1055-9965.epi-18-0654

Cited by 27 publications

(15 citation statements)

References 44 publications

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“…A higher fat content in both cases revealed proinflammatory activity and impaired lipid metabolism [266]. The importance of VAT in the pathogenesis of CRC was not only related to dysregulation of metabolism and changes in inflammatory parameters, but also to proangiogenic effects [267].…”

Section: Lipidsmentioning

confidence: 93%

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

2020

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Background Tumor initiation and subsequent progression are usually long-term processes, spread over time and conditioned by diverse aspects. Many cancers develop on the basis of chronic inflammation; however, despite dozens of years of research, little is known about the factors triggering neoplastic transformation under these conditions. Molecular characterization of both pathogenetic states, i.e., similarities and differences between chronic inflammation and cancer, is also poorly defined. The secretory activity of tumor cells may change the immunophenotype of immune cells and modify the extracellular microenvironment, which allows the bypass of host defense mechanisms and seems to have diagnostic and prognostic value. The phenomenon of immunosuppression is also present during chronic inflammation, and the development of cancer, due to its duration, predisposes patients to the promotion of chronic inflammation. The aim of our work was to discuss the above issues based on the latest scientific insights. A theoretical mechanism of cancer immunosuppression is also proposed. Conclusions Development of solid tumors may occur both during acute and chronic phases of inflammation. Differences in the regulation of immune responses between precancerous states and the cancers resulting from them emphasize the importance of immunosuppressive factors in oncogenesis. Cancer cells may, through their secretory activity and extracellular transport mechanisms, enhance deterioration of the immune system which, in turn, may have prognostic implications.

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Section: Lipidsmentioning

confidence: 93%

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

2020

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“…Ten inflammation biomarkers, including CRP, SAA, TNFα, IL-6, IL-8, monocyte chemoattractant protein 1 (MCP-1), soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1), and angiogenesis-related biomarkers, including VEGF-A and VEGF-D were measured in serum. Previously established assays on the Mesoscale Discovery Platform (MSD), on the Sector 2400A, were used in the Ulrich laboratory at the Huntsman Cancer Institute (27) . Blinded patient samples, intraplate and interplate quality control samples were run on the U-PLEX Proinflammatory Combo 1 for MCP-1, IL-6, IL-8, and TNFα, on the V-PLEX Vascular Injury Plate 2 for CRP, SAA, sICAM-1 and sVCAM-1, and on the V-PLEX Angiogenesis Panel 1 for VEGF-A and VEGF-D. Blinded serum samples were diluted 1:2 (pro-inflammatory panel), 1:1000 (vascular injury plate) and 1:8 (angiogenesis panel).…”

Section: Circulating Inflammation and Angiogenesis Biomarkersmentioning

confidence: 99%

One-carbon metabolites, B vitamins and associations with systemic inflammation and angiogenesis biomarkers among colorectal cancer patients: results from the ColoCare Study

et al. 2020

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B vitamins involved in one-carbon metabolism have been implicated in the development of inflammation- and angiogenesis-related chronic diseases, such as colorectal cancer (CRC). Yet, the role of one-carbon metabolism in inflammation and angiogenesis among CRC patients remains unclear. The objective of this study was to investigate associations of components of one-carbon metabolism with inflammation and angiogenesis biomarkers among newly diagnosed CRC patients (n 238) in the prospective ColoCare Study, Heidelberg. We cross-sectionally analysed associations between twelve B vitamins and one-carbon metabolites and ten inflammation and angiogenesis biomarkers from pre-surgery serum samples using multivariable linear regression models. We further explored associations among novel biomarkers in these pathways with Spearman partial correlation analyses. We hypothesised that pyridoxal-5’-phosphate (PLP) is inversely associated with inflammatory biomarkers. We observed that PLP was inversely associated with C-reactive protein (CRP) (r –0·33, Plinear < 0·0001), serum amyloid A (SAA) (r –0·23, Plinear = 0·003), IL-6 (r –0·39, Plinear < 0·0001), IL-8 (r –0·20, Plinear = 0·02) and TNFα (r –0·12, Plinear = 0·045). Similar findings were observed for 5-methyl-tetrahydrofolate and CRP (r –0·14), SAA (r –0·14) and TNFα (r –0·15) among CRC patients. Folate catabolite acetyl-para-aminobenzoylglutamic acid (pABG) was positively correlated with IL-6 (r 0·27, Plinear < 0·0001), and pABG was positively correlated with IL-8 (r 0·21, Plinear < 0·0001), indicating higher folate utilisation during inflammation. Our data support the hypothesis of inverse associations between PLP and inflammatory biomarkers among CRC patients. A better understanding of the role and inter-relation of PLP and other one-carbon metabolites with inflammatory processes among colorectal carcinogenesis and prognosis could identify targets for future dietary guidance for CRC patients.

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“…Components of the ColoCare Cohort have been leveraged to support initial research; including on biologic determinants of colorectal cancer (e.g., tumor immunity, gut microbiome, epigenome), health behaviors (e.g., physical activity or dietary patterns), components of energy balance (e.g., adipose tissue distribution, accelerometry), clinical endpoints (e.g., surgical complications, quality of life), and novel biomarkers (proteomics, metabolomics, metagenomics). Furthermore, we have published on the interrelations between these factors, specifically in the context of colorectal cancer prognosis (18,(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48). Table 3 highlights research contributions using the growing ColoCare Study cohort.…”

Section: Resultsmentioning

confidence: 99%

The ColoCare Study: A Paradigm of Transdisciplinary Science in Colorectal Cancer Outcomes

Ulrich

Gigic

Böhm

et al. 2019

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Colorectal cancer is a leading cause of cancer death. Biomarkers to predict treatment outcomes are needed, as is evidence whether postdiagnosis diet and lifestyle can affect well-being and clinical outcomes. The international ColoCare Consortium aims to identify new biologic markers (e.g., metabolomic, transcriptomic, metagenomic, genetic, epigenetic, proteomic markers) that predict clinical outcomes, and to characterize associations between modifiable risk factors (e.g., diet, supplement use, physical activity) with shortterm and long-term patient-reported and clinical outcomes among patients with colorectal cancer. Methods/Results: ColoCare is recruiting newly diagnosed patients with colorectal cancer across six sites in the United States and one site in Germany. As of April 2018, we have recruited >2,000 patients across all sites. Our projected enrollment is >4,000 multiethnic patients with colorectal cancer. The study includes uniformly collected, comprehensive sets of data and biospecimens at multiple time points up to 5 years after diagnosis. Treatment and clinical data are abstracted from medical records and centrally harmonized. Biospecimens are archived according to standardized procedures. Our initial studies demonstrated metabolic differences in adipose tissue types. We further reported on associations of biological factors (e.g., inflammation, DNA methylation, metabolomics) with lifestyle factors (e.g., adiposity, smoking, physical activity, dietary supplement use) or joint associations with clinical outcomes. Conclusions: ColoCare is a consortium for the investigation of multilevel factors relevant to colorectal cancer survivorship. Impact: The combination of a comprehensive set of biospecimens collected at multiple time points, jointly with detailed assessments of health behaviors and other prognostic factors, results in a unique resource that facilitates wide-ranging, innovative, and impactful research on colorectal cancer.

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Body Fatness, Adipose Tissue Compartments, and Biomarkers of Inflammation and Angiogenesis in Colorectal Cancer: The ColoCare Study

Cited by 27 publications

References 44 publications

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

One-carbon metabolites, B vitamins and associations with systemic inflammation and angiogenesis biomarkers among colorectal cancer patients: results from the ColoCare Study

The ColoCare Study: A Paradigm of Transdisciplinary Science in Colorectal Cancer Outcomes

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