Inflammation-related plasma protein levels and association with adiposity measurements in young adults

Klevebro, Susanna; Björkander, Sophia; Ekström, Sandra; Merid, Simon Kebede; Gruzieva, Olena; Mälarstig, Anders; Johansson, Åsa; Kull, Inger; Bergström, Anna

doi:10.1038/s41598-021-90843-x

Cited by 13 publications

(16 citation statements)

References 53 publications

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“…Because the present analysis focused on reducing the Proseek multiplex inflammation panel [ 21 ] to the most relevant proteins associated with PPSNP after breast cancer surgery, it was important to define whether the selection represents, in functional terms, the entire panel or only proteins with specific molecular functions within the whole panel. To this end, an enrichment analysis was implemented as an overrepresentation analysis (ORA [ 72 ]) of the annotations to the genes encoding the selected proteins in the Gene Ontology (GO) knowledge base [ 56 ], where the current knowledge about genes is formulated using a controlled vocabulary of GO terms (categories) to which the genes [ 73 ] are annotated [ 74 ].…”

Section: Discussionmentioning

confidence: 99%

“…The details of the assay have been described in detail by Wiberg et al [ 91 ]. In brief, 92 proteins from the Proseek multiplex inflammation panel ( (accessed on 14 March 2022) [ 21 ]) were quantified using a proximity extension assay (PEA) that involves two separate antibodies that bind to the same protein in a sample. Each antibody is coupled to a cDNA strand that is ligated on approach, extended by a polymerase, and finally detected using a Biomark HD 96 real-time dynamic PCR array (Fluidigm, South San Francisco, CA).…”

Section: Methodsmentioning

confidence: 99%

“…Such a cohort was available in a recent study [ 3 , 20 ], from which blood samples had been secured for “omics” analysis before and 4–9 years after the surgery. For this purpose, the Proseek multiplex inflammation panel [ 21 ] was selected as a collection of inflammation- and immune-related proteins for which associations with pain or cancer had already been reported in other clinical settings [ 22 , 23 ]. The present analysis of these new proteomics data pursued the hypothesis that breast cancer surgery-related neuropathic pain is reflected in a specific proteomics pattern.…”

Section: Introductionmentioning

confidence: 99%

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Machine-Learning Analysis of Serum Proteomics in Neuropathic Pain after Nerve Injury in Breast Cancer Surgery Points at Chemokine Signaling via SIRT2 Regulation

Lötsch

Mustonen

Harno

et al. 2022

IJMS

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Background: Persistent postsurgical neuropathic pain (PPSNP) can occur after intraoperative damage to somatosensory nerves, with a prevalence of 29–57% in breast cancer surgery. Proteomics is an active research field in neuropathic pain and the first results support its utility for establishing diagnoses or finding therapy strategies. Methods: 57 women (30 non-PPSNP/27 PPSNP) who had experienced a surgeon-verified intercostobrachial nerve injury during breast cancer surgery, were examined for patterns in 74 serum proteomic markers that allowed discrimination between subgroups with or without PPSNP. Serum samples were obtained both before and after surgery. Results: Unsupervised data analyses, including principal component analysis and self-organizing maps of artificial neurons, revealed patterns that supported a data structure consistent with pain-related subgroup (non-PPSPN vs. PPSNP) separation. Subsequent supervised machine learning-based analyses revealed 19 proteins (CD244, SIRT2, CCL28, CXCL9, CCL20, CCL3, IL.10RA, MCP.1, TRAIL, CCL25, IL10, uPA, CCL4, DNER, STAMPB, CCL23, CST5, CCL11, FGF.23) that were informative for subgroup separation. In cross-validated training and testing of six different machine-learned algorithms, subgroup assignment was significantly better than chance, whereas this was not possible when training the algorithms with randomly permuted data or with the protein markers not selected. In particular, sirtuin 2 emerged as a key protein, presenting both before and after breast cancer treatments in the PPSNP compared with the non-PPSNP subgroup. Conclusions: The identified proteins play important roles in immune processes such as cell migration, chemotaxis, and cytokine-signaling. They also have considerable overlap with currently known targets of approved or investigational drugs. Taken together, several lines of unsupervised and supervised analyses pointed to structures in serum proteomics data, obtained before and after breast cancer surgery, that relate to neuroinflammatory processes associated with the development of neuropathic pain after an intraoperative nerve lesion.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Machine-Learning Analysis of Serum Proteomics in Neuropathic Pain after Nerve Injury in Breast Cancer Surgery Points at Chemokine Signaling via SIRT2 Regulation

Lötsch

Mustonen

Harno

et al. 2022

IJMS

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“…Data on specific IgE, eosinophil, and neutrophil counts were available from clinical follow-ups ( 14 ). Finally, 92 inflammation-related protein biomarkers (Table E10) were measured in plasma by Proseek Multiplex Inflammation I panel (Olink Bioscience) at 24 years ( 27 ).…”

Section: Methodsmentioning

confidence: 99%

Plasticity of Individual Lung Function States from Childhood to Adulthood

Wang

Hallberg

Faner

et al. 2023

Am J Respir Crit Care Med

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Rationale Recent evidence highlights the importance of optimal lung development during childhood for health throughout life. Objectives To explore the plasticity of individual lung function states during childhood. Methods Prebronchodilator FEV 1 z -scores determined at age 8, 16, and 24 years in the Swedish population-based birth cohort BAMSE (Swedish abbreviation for Child [Barn], Allergy, Milieu, Stockholm, Epidemiological study) ( N = 3,069) were used. An unbiased, data-driven dependent mixture model was applied to explore lung function states and individual state chains. Lung function catch-up was defined as participants moving from low or very low states to normal or high or very high states, and growth failure as moving from normal or high or very high states to low or very low states. At 24 years, we compared respiratory symptoms, small airway function (multiple-breath washout), and circulating inflammatory protein levels, by using proteomics, across states. Models were replicated in the independent Dutch population-based PIAMA (Prevention and Incidence of Asthma and Mite Allergy) cohort. Measurements and Main Results Five lung function states were identified in BAMSE. Lung function catch-up and growth failure were observed in 74 (14.5%) BAMSE participants with low or very low states and 36 (2.4%) participants with normal or high or very high states, respectively. The occurrence of catch-up and growth failure was replicated in PIAMA. Early-life risk factors were cumulatively associated with the very low state, as well as with catch-up (inverse association) and growth failure. The very low state as well as growth failure were associated with respiratory symptoms, airflow limitation, and small airway dysfunction at adulthood. Proteomics identified IL-6 and CXCL10 (C-X-C motif chemokine 10) as potential biomarkers of impaired lung function development. Conclusions Individual lung function states during childhood are plastic, including catch-up and growth failure.

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“…В настоящее время установлено, что нарушение лимфатического дренажа при ожирении тесно связано с развитием латентного (низкоинтенсивного) воспаления ЖТ. Корреляция между массой ЖТ с уровнем циркулирующих маркеров воспаления была показана в общепопуляционных исследованиях [43,44], а также у больных сахарным диабетом 2 типа [45,46]. В настоящее время хроническое воспаление ЖТ рассматривается как важный механизм в развитии инсулинорезистентности.…”

Section: взаимодействия между лимфатической системой и жировой тканью при ожиренииunclassified

Lymphatic system and adipose tissue: Crosstalk in health and disease

Климонтов

Bulumbaeva

2021

Obes. metabol.

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The lymphatic system (LS) is one of the main integrative systems of the body, providing protective and transport functions. In recent years, interactions between LS and adipose tissue (AT) have been of particular interest. Lymphatic vessels play an important role in metabolic and regulatory functions of AT, acting as a collector of lipolysis products and adipokines. In its turn, hormones and adipocytokines that produced in adipocytes (including leptin, adiponectin, IL-6, TNF-α, etc.) affect the function of lymphatic endothelial cells and control the growth of lymphatic vessels. Cooperation between LS and AT becomes pathogenetically and clinically important in lymphedema and obesity. It is known that both primary and secondary lymphedema are characterized by increased fat accumulation which is associated with the severity of lymphostasis and inflammation. Similarly, in obesity, the drainage function of LS is impaired, which is accompanied by perilymphatic mononuclear infiltration in the AT. The development of these changes is facilitated by endocrine dysfunction of adipocytes and impaired production of adipocytokines. The increase in the production of inflammatory mediators and the disruption of the traffic of inflammatory cells causes a further deterioration in the outflow of interstitial fluid and exacerbates the inflammation of the AT, thereby forming a vicious circle. The role of lymphangiogenesis in AT remodeling in obesity needs further research. Another promising area of research is the study of the role of intestinal LS in the development of obesity and related disorders. It has been shown that the transport of chylomicrons from the intestine depends on the expression of a number of molecular mediators (VEGF-C, DLL-4, neuropilin-1, VEGFR-1, CD36/FAT, etc.)in the endotheliocytes of the intestinal lymphatic vessels, as well as the functioning of «push-button» and “zippering” junctions between endothelial cells. New approach to the treatment of obesity based on blockade of lymphatic chylomicrontransport has been experimentally substantiated. Further identification of the molecular mechanisms and signaling pathways that determine the remodeling of AT in lymphedema and obesity are likely to provide new approaches to the treatment of these diseases.

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Inflammation-related plasma protein levels and association with adiposity measurements in young adults

Cited by 13 publications

References 53 publications

Machine-Learning Analysis of Serum Proteomics in Neuropathic Pain after Nerve Injury in Breast Cancer Surgery Points at Chemokine Signaling via SIRT2 Regulation

Machine-Learning Analysis of Serum Proteomics in Neuropathic Pain after Nerve Injury in Breast Cancer Surgery Points at Chemokine Signaling via SIRT2 Regulation

Plasticity of Individual Lung Function States from Childhood to Adulthood

Lymphatic system and adipose tissue: Crosstalk in health and disease

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