Dataset Information

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

ABSTRACT: BACKGROUND:Adiposity has been linked to both risk and prognosis of colorectal cancer; however, the impact of different fat areas [visceral (VFA) vs. subcutaneous fat area (SFA)] is unclear. We investigated associations between adiposity and biomarkers of inflammation and angiogenesis among patients with colorectal cancer. METHODS:Preoperative serum samples and computed tomography scans were obtained from 188 patients diagnosed with primary invasive stage I-IV colorectal cancer enrolled in the ColoCare Study. Adiposity was assessed by area-based quantification of VFA, SFA, and VFA:SFA ratio on spinal levels L3/L4 and L4/L5. Circulating levels of inflammation (CRP, SAA, sICAM-1, and sVCAM-1) and angiogenesis (VEGF-A and VEGF-D) were assessed from patient sera on the Meso Scale Discovery platform. Partial correlations and regression analyses, adjusted for age, sex, and tumor stage, were performed. RESULTS:VFA was moderately correlated with CRP and SAA (CRP: L3/L4 and L4/L5:r = 0.21, P = 0.01; SAA: L3/L4:r = 0.17, P = 0.04). The correlation between SFA and the measured biomarkers were weak (r ? 0.13, not significant). The ratio of VFA:SFA at L3/L4 was moderately correlated with VEGF-A (r = 0.28, P = 0.0008) and SAA (r = 0.24, P = 0.006), and less so with CRP (r = 0.18, P = 0.04) and sICAM-1 (r = 0.18, P = 0.04). Similar correlations were found for the VFA:SFA ratio at L4/L5. CONCLUSIONS:We observed an association between visceral adiposity and biomarkers of inflammation and angiogenesis in colorectal cancer. In particular, the VFA:SFA ratio was correlated with circulating levels of the proangiogenic biomarker VEGF-A. IMPACT:Our findings support a direct association of visceral adipose tissue with inflammatory and angiogenic processes, which play fundamental roles in the development and progression of colorectal cancer.

SUBMITTER: Himbert C

PROVIDER: S-EPMC6324954 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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

Himbert Caroline C Ose Jennifer J Nattenmüller Johanna J Warby Christy A CA Holowatyj Andreana N AN Böhm Jürgen J Lin Tengda T Haffa Mariam M Gigic Biljana B Hardikar Sheetal S Scherer Dominique D Zielske Lin L Schrotz-King Petra P Kölsch Torsten T Siegel Erin M EM Shibata David D Ulrich Alexis A Schneider Martin M Hursting Stephen D SD Kauczor Hans-Ulrich HU Ulrich Cornelia M CM

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20181017 1

<h4>Background</h4>Adiposity has been linked to both risk and prognosis of colorectal cancer; however, the impact of different fat areas [visceral (VFA) vs. subcutaneous fat area (SFA)] is unclear. We investigated associations between adiposity and biomarkers of inflammation and angiogenesis among patients with colorectal cancer.<h4>Methods</h4>Preoperative serum samples and computed tomography scans were obtained from 188 patients diagnosed with primary invasive stage I-IV colorectal cancer enr ...[more]

PMID: 30333223

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Project description: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.

Project description:BackgroundMetabolic and transcriptomic differences between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) compartments, particularly in the context of obesity, may play a role in colorectal carcinogenesis. We investigated the differential functions of their metabolic compositions.ObjectivesBiochemical differences between adipose tissues (VAT compared with SAT) in patients with colorectal carcinoma (CRC) were investigated by using mass spectrometry metabolomics and gene expression profiling. Metabolite compositions were compared between VAT, SAT, and serum metabolites. The relation between patients' tumor stage and metabolic profiles was assessed.DesignPresurgery blood and paired VAT and SAT samples during tumor surgery were obtained from 59 CRC patients (tumor stages I-IV) of the ColoCare cohort. Gas chromatography time-of-flight mass spectrometry and liquid chromatography quadrupole time-of-flight mass spectrometry were used to measure 1065 metabolites in adipose tissue (333 identified compounds) and 1810 metabolites in serum (467 identified compounds). Adipose tissue gene expression was measured by using Illumina's HumanHT-12 Expression BeadChips.ResultsCompared with SAT, VAT displayed elevated markers of inflammatory lipid metabolism, free arachidonic acid, phospholipases (PLA2G10), and prostaglandin synthesis-related enzymes (PTGD/PTGS2S). Plasmalogen concentrations were lower in VAT than in SAT, which was supported by lower gene expression of FAR1, the rate-limiting enzyme for ether-lipid synthesis in VAT. Serum sphingomyelin concentrations were inversely correlated (P = 0.0001) with SAT adipose triglycerides. Logistic regression identified lipids in patients' adipose tissues, which were associated with CRC tumor stage.ConclusionsAs one of the first studies, we comprehensively assessed differences in metabolic, lipidomic, and transcriptomic profiles between paired human VAT and SAT and their association with CRC tumor stage. We identified markers of inflammation in VAT, which supports prior evidence regarding the role of visceral adiposity and cancer.

Project description:PurposeWhile obesity is considered a prognostic factor in colorectal cancer (CRC), there is increasing evidence that not simply body mass index (BMI) alone but specifically abdominal fat distribution is what matters. As part of the ColoCare study, this study measured the distribution of adipose tissue compartments in CRC patients and aimed to identify the body metric that best correlates with these measurements as a useful proxy for adipose tissue distribution.Materials and methodsIn 120 newly-diagnosed CRC patients who underwent multidetector computed tomography (CT), densitometric quantification of total (TFA), visceral (VFA), intraperitoneal (IFA), retroperitoneal (RFA), and subcutaneous fat area (SFA), as well as the M. erector spinae and psoas was performed to test the association with gender, age, tumor stage, metabolic equivalents, BMI, waist-to-height (WHtR) and waist-to-hip ratio (WHR).ResultsVFA was 28.8 % higher in men (pVFA<0.0001) and 30.5 % higher in patients older than 61 years (pVFA<0.0001). WHtR correlated best with all adipose tissue compartments (rVFA=0.69, rTFA=0.84, p<0.0001) and visceral-to-subcutaneous-fat-ratio (VFR, rVFR=0.22, p=<0.05). Patients with tumor stages III/IV showed significantly lower overall adipose tissue than I/II. Increased M. erector spinae mass was inversely correlated with all compartments.ConclusionDensitometric quantification on CT is a highly reproducible and reliable method to show fat distribution across adipose tissue compartments. This distribution might be best reflected by WHtR, rather than by BMI or WHR.Key points• Densitometric quantification of adipose tissue on CT is highly reproducible and reliable. • Waist-to-height ratio better correlates with adipose tissue compartments and VFR than BMI or waist-to-hip ratio. • Men have higher a higher visceral fat area than women. • Patients older than 61 years have higher visceral fat area. • Patients with tumor stages III/IV have significantly lower adipose tissue than those in stages I/II.

Project description:PurposeTo enable fast and reliable assessment of subcutaneous and visceral adipose tissue compartments derived from whole-body MRI.Materials and methodsQuantification and localization of different adipose tissue compartments derived from whole-body MR images is of high interest in research concerning metabolic conditions. For correct identification and phenotyping of individuals at increased risk for metabolic diseases, a reliable automated segmentation of adipose tissue into subcutaneous and visceral adipose tissue is required. In this work, a three-dimensional (3D) densely connected convolutional neural network (DCNet) is proposed to provide robust and objective segmentation. In this retrospective study, 1000 cases (average age, 66 years ± 13 [standard deviation]; 523 women) from the Tuebingen Family Study database and the German Center for Diabetes research database and 300 cases (average age, 53 years ± 11; 152 women) from the German National Cohort (NAKO) database were collected for model training, validation, and testing, with transfer learning between the cohorts. These datasets included variable imaging sequences, imaging contrasts, receiver coil arrangements, scanners, and imaging field strengths. The proposed DCNet was compared to a similar 3D U-Net segmentation in terms of sensitivity, specificity, precision, accuracy, and Dice overlap.ResultsFast (range, 5-7 seconds) and reliable adipose tissue segmentation can be performed with high Dice overlap (0.94), sensitivity (96.6%), specificity (95.1%), precision (92.1%), and accuracy (98.4%) from 3D whole-body MRI datasets (field of view coverage, 450 × 450 × 2000 mm). Segmentation masks and adipose tissue profiles are automatically reported back to the referring physician.ConclusionAutomated adipose tissue segmentation is feasible in 3D whole-body MRI datasets and is generalizable to different epidemiologic cohort studies with the proposed DCNet.Supplemental material is available for this article.© RSNA, 2020.

Dataset Information

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

Publications

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

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